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Erschienen in: Neurotoxicity Research 1/2015

01.01.2015 | Review

DSP4, a Selective Neurotoxin for the Locus Coeruleus Noradrenergic System. A Review of Its Mode of Action

verfasst von: Svante B. Ross, Carina Stenfors

Erschienen in: Neurotoxicity Research | Ausgabe 1/2015

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Abstract

DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) is a selective neurotoxin for the locus coeruleus noradrenergic system in the rodent and bird brain. It readily passes the blood–brain barrier and cyclizes to a reactive aziridinium derivative that is accumulated into the noradrenergic nerve terminals via the noradrenaline transporter. DSP4 is also an irreversible inhibitor of this transporter. Within the nerve terminals the aziridinium derivative reacts with unknown vital cellular components, destroying the terminals. At the dose 50 mg/kg i.p. this is characterized by a rapid and long-lasting loss of noradrenaline and a slower decrease in the dopamine-β-hydroxylase enzyme activity and immunoreactivity in the regions innervated from locus coeruleus. The tissue level of noradrenaline is reduced to 10–30 % of the normal value. The extraneuronal concentration is, on the other hand, increased due to inflow from non-lesioned regions. Like the peripheral sympathetic nerves the non-locus coeruleus noradrenergic systems in the rodent brain is resistant to the neurotoxic action of DSP4. Serotoninergic and dopaminergic nerves are only slightly or not at all affected by DSP4. The neurotoxic effect is counteracted by pretreatment with noradrenaline uptake inhibitors (e.g., desipramine). MAO-B inhibitors of the N-propargylamine type (e.g., selegiline) also counteract the DSP4-induced neurotoxicity with another, yet unknown mechanism. Because of its selectivity for the locus coeruleus system DSP4 is a useful tool in studies of the functional role of this noradrenergic system in the brain.
Fußnoten
1
Why the name DSP4? At that time the Astra chemists named their new substances with a three-letters code which was characteristic of each series of compounds. In this case: D is for Dahlbom, Richard, the chemist, S for Svante Ross, P for Psychopharmacology, the intended use, and this compound was the fourth in the series, including intermediates.
 
Literatur
Zurück zum Zitat Alttoa A, Kölv K, Eller M, Uustare A, Rinken A, Harro J (2005) Effects of low doses of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administrated on exploratory and amphetamine-induced behavior and dopamine D2 receptor function in rats with high or low exploratory activity. Neuroscience 132:979–990PubMed Alttoa A, Kölv K, Eller M, Uustare A, Rinken A, Harro J (2005) Effects of low doses of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administrated on exploratory and amphetamine-induced behavior and dopamine D2 receptor function in rats with high or low exploratory activity. Neuroscience 132:979–990PubMed
Zurück zum Zitat Archer T, Fredriksson A (2001) Effects of alpha-adrenoceptor agonists in chronic morphine administered DSP4-treated rats: evidence for functional cross-sensitization. Neurotox Res 3:411–432PubMed Archer T, Fredriksson A (2001) Effects of alpha-adrenoceptor agonists in chronic morphine administered DSP4-treated rats: evidence for functional cross-sensitization. Neurotox Res 3:411–432PubMed
Zurück zum Zitat Archer T, Jonsson G, Ross SB (1984) A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurons in the CNS of the rat. Br J Pharmacol 82:249–257PubMedCentralPubMed Archer T, Jonsson G, Ross SB (1984) A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurons in the CNS of the rat. Br J Pharmacol 82:249–257PubMedCentralPubMed
Zurück zum Zitat Asin KE, Wirtshafter D, Fibiger HC (1982) Alteration in drug induced catalepsy and post-decapitation convulsions following brain and spinal cord depletion of norepinephrine by the neurotoxin DSP-4. Life Sci 30:1531–1536PubMed Asin KE, Wirtshafter D, Fibiger HC (1982) Alteration in drug induced catalepsy and post-decapitation convulsions following brain and spinal cord depletion of norepinephrine by the neurotoxin DSP-4. Life Sci 30:1531–1536PubMed
Zurück zum Zitat Barclay SR, Harding CF, Waterman SA (1996) Central DSP-4 treatment decreases norepinephrine levels and courtship behavior in male zebra finches. Pharmacol Biochem Behav 53:213–220PubMed Barclay SR, Harding CF, Waterman SA (1996) Central DSP-4 treatment decreases norepinephrine levels and courtship behavior in male zebra finches. Pharmacol Biochem Behav 53:213–220PubMed
Zurück zum Zitat Bitler CM, Zhang MB, Howard BD (1986) PC12 variants deficient in catecholamine transport. J Neurochem 47:1286–1293PubMed Bitler CM, Zhang MB, Howard BD (1986) PC12 variants deficient in catecholamine transport. J Neurochem 47:1286–1293PubMed
Zurück zum Zitat Booze RM, Hall JA, Cress NM, Miller GD, Davis JN (1988) DSP-4 treatment produces abnormal tyrosine hydroxylase immunoactive fibers in rat hippocampus. Exp Neurol 101:75–86PubMed Booze RM, Hall JA, Cress NM, Miller GD, Davis JN (1988) DSP-4 treatment produces abnormal tyrosine hydroxylase immunoactive fibers in rat hippocampus. Exp Neurol 101:75–86PubMed
Zurück zum Zitat Bortel A (2014) Nature of DSP-4-induced neurotoxicity. In: Kostrzewa RM (ed) Handbook of neurotoxicity. Springer, New York, pp 221–236 Bortel A (2014) Nature of DSP-4-induced neurotoxicity. In: Kostrzewa RM (ed) Handbook of neurotoxicity. Springer, New York, pp 221–236
Zurück zum Zitat Bortel A, Nowak P, Brus R (2008) Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex in adult rats. Neurotox Res 13:247–252PubMed Bortel A, Nowak P, Brus R (2008) Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex in adult rats. Neurotox Res 13:247–252PubMed
Zurück zum Zitat Bortolozzi A, Artigas F (2006) Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors. Neuropsychopharmacology 28:421–434 Bortolozzi A, Artigas F (2006) Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors. Neuropsychopharmacology 28:421–434
Zurück zum Zitat Cassano T, Gaetani S, Morgese MG, Macheda T, Laconca L, Dispaquale P, Taltavull J, Shippenberg TS, Cuomo V, Gobbi G (2010) Monoaminergic changes in locus coeruleus and dorsal raphe nucleus following noradrenaline depletion. Neurochem Res 34:1417–1426 Cassano T, Gaetani S, Morgese MG, Macheda T, Laconca L, Dispaquale P, Taltavull J, Shippenberg TS, Cuomo V, Gobbi G (2010) Monoaminergic changes in locus coeruleus and dorsal raphe nucleus following noradrenaline depletion. Neurochem Res 34:1417–1426
Zurück zum Zitat Casteling CB, Schmidt MF (2010) What birdsong can teach us about the central noradrenergic system? J Chem Neuroanat 39:96–111 Casteling CB, Schmidt MF (2010) What birdsong can teach us about the central noradrenergic system? J Chem Neuroanat 39:96–111
Zurück zum Zitat Cheetham SC, Viggers JA, Butler SA, Prow MR, Heal DJ (1996) [3H]nisoxetine—a radioligand for noradrenaline reuptake site: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatment. Neuropharmacology 35:63–70PubMed Cheetham SC, Viggers JA, Butler SA, Prow MR, Heal DJ (1996) [3H]nisoxetine—a radioligand for noradrenaline reuptake site: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatment. Neuropharmacology 35:63–70PubMed
Zurück zum Zitat Cho AK, Ransom RW, Fischer JB, Kammerer RC (1980) The effects of xylamine, a nitrogen mustard on [3H]norepinephrine accumulation in rabbit aorta. J Pharmacol Exp Ther 214:324–327PubMed Cho AK, Ransom RW, Fischer JB, Kammerer RC (1980) The effects of xylamine, a nitrogen mustard on [3H]norepinephrine accumulation in rabbit aorta. J Pharmacol Exp Ther 214:324–327PubMed
Zurück zum Zitat Cushing SD (1988) Characterization of the binding of xylamine, an irreversible inhibitor of the catecholamine transporter and depletor of neuronal noradrenergic stores. PhD Thesis, University of California, LA, 212 pp Cushing SD (1988) Characterization of the binding of xylamine, an irreversible inhibitor of the catecholamine transporter and depletor of neuronal noradrenergic stores. PhD Thesis, University of California, LA, 212 pp
Zurück zum Zitat Dabrowska J, Nowak P, Brus R (2007) Desensitization of 5-HT1A autoreceptors induced by neonatal DSP-4 treatment. Eur Neuropsychopharmacol 17:129–137PubMed Dabrowska J, Nowak P, Brus R (2007) Desensitization of 5-HT1A autoreceptors induced by neonatal DSP-4 treatment. Eur Neuropsychopharmacol 17:129–137PubMed
Zurück zum Zitat Danysz W, Jonsson G, Mohammed AK, Archer T (1985) The hind limb extension reflex is not a reliable marker of post-decapitation convulsions or spinal noradrenaline depletion in rats. Eur J Pharmacol 116:331–333PubMed Danysz W, Jonsson G, Mohammed AK, Archer T (1985) The hind limb extension reflex is not a reliable marker of post-decapitation convulsions or spinal noradrenaline depletion in rats. Eur J Pharmacol 116:331–333PubMed
Zurück zum Zitat Davies DC, Horn G, McGabe BJ (1985) Noradrenaline and learning: effects of the noradrenergic neurotoxin DSP4 on inprinting in the domestic chick. Behav Neurosci 89:652–660 Davies DC, Horn G, McGabe BJ (1985) Noradrenaline and learning: effects of the noradrenergic neurotoxin DSP4 on inprinting in the domestic chick. Behav Neurosci 89:652–660
Zurück zum Zitat Delagrange P, Tadjer D, Bouyer JJ, Rougeul A, Conrath M (1989) Effect of DSP4, a neurotoxic agent, on alternative behaviour and related electrocortical activity in cat. Behav Brain Res 33:33–43PubMed Delagrange P, Tadjer D, Bouyer JJ, Rougeul A, Conrath M (1989) Effect of DSP4, a neurotoxic agent, on alternative behaviour and related electrocortical activity in cat. Behav Brain Res 33:33–43PubMed
Zurück zum Zitat Dudley MW (1988) The depletion of rat cortical norepinephrine and the inhibition of [3H] norepinephrine uptake by xylamine does not require monoamine oxidase activity. Life Sci 43:1871–1877PubMed Dudley MW (1988) The depletion of rat cortical norepinephrine and the inhibition of [3H] norepinephrine uptake by xylamine does not require monoamine oxidase activity. Life Sci 43:1871–1877PubMed
Zurück zum Zitat Dudley MW, Butcher LL, Kammerer RC, Cho AK (1981) The actions of xylamine on central noradrenergic neurons. J Pharmacol Exp Ther 217:834–840PubMed Dudley MW, Butcher LL, Kammerer RC, Cho AK (1981) The actions of xylamine on central noradrenergic neurons. J Pharmacol Exp Ther 217:834–840PubMed
Zurück zum Zitat Dudley MW, Howard BD, Cho AK (1990) The interaction of the beta-haloethylbenzylamines, xylamine and DSP-4 with catecholaminergic neurons. Ann Rev Pharmacol Toxicol 30:387–403 Dudley MW, Howard BD, Cho AK (1990) The interaction of the beta-haloethylbenzylamines, xylamine and DSP-4 with catecholaminergic neurons. Ann Rev Pharmacol Toxicol 30:387–403
Zurück zum Zitat Féty R, Misére V, Lambás-Senas L, Renaud B (1986) Central and peripheral changes in catecholamine-synthesizing enzyme activities after systemic administration of the neurotoxin DSP-4. Eur J Pharmacol 124:197–202PubMed Féty R, Misére V, Lambás-Senas L, Renaud B (1986) Central and peripheral changes in catecholamine-synthesizing enzyme activities after systemic administration of the neurotoxin DSP-4. Eur J Pharmacol 124:197–202PubMed
Zurück zum Zitat Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langston JW (1990) Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO B. Eur J Pharmacol 184:119–126PubMed Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langston JW (1990) Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO B. Eur J Pharmacol 184:119–126PubMed
Zurück zum Zitat Fischer JB, Waggaman LA, Ransom RW, Cho AK (1983) Xylamine, an irreversible inhibitor of norepinephrine uptake, is transported by the same uptake mechanism in cultured rat superior ganglia. J Pharmacol Exp Ther 226:650–655PubMed Fischer JB, Waggaman LA, Ransom RW, Cho AK (1983) Xylamine, an irreversible inhibitor of norepinephrine uptake, is transported by the same uptake mechanism in cultured rat superior ganglia. J Pharmacol Exp Ther 226:650–655PubMed
Zurück zum Zitat Fornai F, Bassi L, Torracca MT, Alessandri MG, Scalori V, Corsini GU (1996) Region- and neurotransmitter dependent species and strain differences in DSP-4-induced monoamine depletion in rodents. Neurodegeneration 5:241–249PubMed Fornai F, Bassi L, Torracca MT, Alessandri MG, Scalori V, Corsini GU (1996) Region- and neurotransmitter dependent species and strain differences in DSP-4-induced monoamine depletion in rodents. Neurodegeneration 5:241–249PubMed
Zurück zum Zitat Fornai F, Giorgi FS, Gesi M, Chen K, Alessi MG, Shih JC (2001) Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice. Synapse 38:213–221 Fornai F, Giorgi FS, Gesi M, Chen K, Alessi MG, Shih JC (2001) Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice. Synapse 38:213–221
Zurück zum Zitat Fritschy JM, Grzanna R (1989) Immunochemically analysis of the neurotoxic effects of DSP-4 identifies two populations of noradrenergic axon terminals. Neuroscience 30:181–197PubMed Fritschy JM, Grzanna R (1989) Immunochemically analysis of the neurotoxic effects of DSP-4 identifies two populations of noradrenergic axon terminals. Neuroscience 30:181–197PubMed
Zurück zum Zitat Fritschy JM, Grzanna R (1990) Demonstration of two separate descending noradrenergic pathways in the rat spinal cord: evidence for an intragriseal trajectory of locus coeruleus axons in the superficial layers of the dorsal horn. J Comp Neurol 291:553–582PubMed Fritschy JM, Grzanna R (1990) Demonstration of two separate descending noradrenergic pathways in the rat spinal cord: evidence for an intragriseal trajectory of locus coeruleus axons in the superficial layers of the dorsal horn. J Comp Neurol 291:553–582PubMed
Zurück zum Zitat Fritschy JM, Grzanna R (1991a) Experimentally-induced neuron loss in the locus coeruleus of adult rats. Exp Neurol 111:123–127PubMed Fritschy JM, Grzanna R (1991a) Experimentally-induced neuron loss in the locus coeruleus of adult rats. Exp Neurol 111:123–127PubMed
Zurück zum Zitat Fritschy JM, Grzanna R (1991b) Selective effects of DSP-4 on locus coeruleus axons: are there pharmacologically different types of noradrenergic axons in the central nervous system? Prog Brain Res 88:257–268PubMed Fritschy JM, Grzanna R (1991b) Selective effects of DSP-4 on locus coeruleus axons: are there pharmacologically different types of noradrenergic axons in the central nervous system? Prog Brain Res 88:257–268PubMed
Zurück zum Zitat Fritschy JM, Grzanna R (1992) Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: compensatory response to neurotoxin-induced cell death in the adult rat brain. J Comp Neurol 321:421–441PubMed Fritschy JM, Grzanna R (1992) Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: compensatory response to neurotoxin-induced cell death in the adult rat brain. J Comp Neurol 321:421–441PubMed
Zurück zum Zitat Fritschy JM, Geffard M, Grzanna R (1990) The response of noradrenergic axons to systematically administered DSP-4 in the rat: an immunohistochemically study using antibodies to noradrenaline and dopamine-beta-hydroxylase. J Chem Neuroanal 3:309–321 Fritschy JM, Geffard M, Grzanna R (1990) The response of noradrenergic axons to systematically administered DSP-4 in the rat: an immunohistochemically study using antibodies to noradrenaline and dopamine-beta-hydroxylase. J Chem Neuroanal 3:309–321
Zurück zum Zitat Furchgott RF, Garcia PS, Wakade AR, Cervoni P (1971) Interactions of bretylium and other drugs on guinea-pig atria: evidence for inhibition of neuronal monoamine oxidase by bretylium. J Pharmacol Exp Ther 179:171–185PubMed Furchgott RF, Garcia PS, Wakade AR, Cervoni P (1971) Interactions of bretylium and other drugs on guinea-pig atria: evidence for inhibition of neuronal monoamine oxidase by bretylium. J Pharmacol Exp Ther 179:171–185PubMed
Zurück zum Zitat Gibson CJ (1987) Inhibition of MAO B, but not MAO A, blocks DSP-4 toxicity on central NE neurons. Eur J Pharmacol 14:135–138 Gibson CJ (1987) Inhibition of MAO B, but not MAO A, blocks DSP-4 toxicity on central NE neurons. Eur J Pharmacol 14:135–138
Zurück zum Zitat Grzanna R, Berger U, Fritschy JM, Geffard M (1989) Acute action of DSP-4 on central norepinephrine axons: biochemical and immunohistochemical evidence for differential effects. J Histochem Cytochem 37:1435–1442PubMed Grzanna R, Berger U, Fritschy JM, Geffard M (1989) Acute action of DSP-4 on central norepinephrine axons: biochemical and immunohistochemical evidence for differential effects. J Histochem Cytochem 37:1435–1442PubMed
Zurück zum Zitat Haberle D, Szöko E, Hajász AS, Magyar K (2001) The effect of a low dose of (−)-deprenyl and its metabolites on DSP-4 toxicity. J Neural Transm 108:1237–1239 Haberle D, Szöko E, Hajász AS, Magyar K (2001) The effect of a low dose of (−)-deprenyl and its metabolites on DSP-4 toxicity. J Neural Transm 108:1237–1239
Zurück zum Zitat Haberle D, Magyar K, Szökö E (2002) Determination of the norepinephrine level by high-performance liquid chromatography to assess the protective effect of MAO-B inhibitors against DSP-4 toxicity. J Chromatogr Sci 40:495–499PubMed Haberle D, Magyar K, Szökö E (2002) Determination of the norepinephrine level by high-performance liquid chromatography to assess the protective effect of MAO-B inhibitors against DSP-4 toxicity. J Chromatogr Sci 40:495–499PubMed
Zurück zum Zitat Hallman H, Jonsson G (1984) Pharmacological modification of the neurotoxic action of the noradrenaline neurotoxin DSP4 on central noradrenaline neurons. Eur J Pharmacol 103:269–278PubMed Hallman H, Jonsson G (1984) Pharmacological modification of the neurotoxic action of the noradrenaline neurotoxin DSP4 on central noradrenaline neurons. Eur J Pharmacol 103:269–278PubMed
Zurück zum Zitat Hallman H, Sundström E, Jonsson G (1984) Effects of the noradrenaline neurotoxin DSP4 on monoamine neurons and their transmitter turnover in rat CNS. J Neural Transm 60:89–102PubMed Hallman H, Sundström E, Jonsson G (1984) Effects of the noradrenaline neurotoxin DSP4 on monoamine neurons and their transmitter turnover in rat CNS. J Neural Transm 60:89–102PubMed
Zurück zum Zitat Harro J, Pähkla R, Modiiri A-R, Harro M, Kask A, Oreland L (1999) Dose-dependent effects of noradrenergic denervation by DSP-4 treatment on forced swimming and beta-adrenoceptor binding in the rat. J Neural Transm 106:619–629PubMed Harro J, Pähkla R, Modiiri A-R, Harro M, Kask A, Oreland L (1999) Dose-dependent effects of noradrenergic denervation by DSP-4 treatment on forced swimming and beta-adrenoceptor binding in the rat. J Neural Transm 106:619–629PubMed
Zurück zum Zitat Hatip-Al-Khatib I, Mishima K, Iwasaki K, Fujiwara M (2001) Microdialysates of amines and metabolites from core nucleus accumbens of freely moving rats are altered by dizocilpine. Brain Res 902:108–118PubMed Hatip-Al-Khatib I, Mishima K, Iwasaki K, Fujiwara M (2001) Microdialysates of amines and metabolites from core nucleus accumbens of freely moving rats are altered by dizocilpine. Brain Res 902:108–118PubMed
Zurück zum Zitat Heal DJ, Butler SA, Prow MR, Buckett WR (1993) Quantification of presynaptic alpha-2-adrenoceptors in rat brain after short-term DSP-4 lesioning. Eur J Pharmacol 249:37–41PubMed Heal DJ, Butler SA, Prow MR, Buckett WR (1993) Quantification of presynaptic alpha-2-adrenoceptors in rat brain after short-term DSP-4 lesioning. Eur J Pharmacol 249:37–41PubMed
Zurück zum Zitat Holt A, Berry MD, Boulton AA (2004) On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site. And effects thereby elicited. Neurotoxicology 25:251–266PubMed Holt A, Berry MD, Boulton AA (2004) On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site. And effects thereby elicited. Neurotoxicology 25:251–266PubMed
Zurück zum Zitat Hormigo S, Horta Junior JD, Gômez-Neto R, Lôpez DE (2012) The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats. Front Neural Circuits 6:41PubMedCentralPubMed Hormigo S, Horta Junior JD, Gômez-Neto R, Lôpez DE (2012) The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats. Front Neural Circuits 6:41PubMedCentralPubMed
Zurück zum Zitat Howard BD, Cho AK, Zhang MB, Koide M, Lin S (1990) Covalent labeling of the cocaine-sensitive catecholamine transporter. J Neurosci Res 26:149–158PubMed Howard BD, Cho AK, Zhang MB, Koide M, Lin S (1990) Covalent labeling of the cocaine-sensitive catecholamine transporter. J Neurosci Res 26:149–158PubMed
Zurück zum Zitat Hughes ZA, Stanford SC (1998a) Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs. Br J Pharmacol 124:1141–1148PubMedCentralPubMed Hughes ZA, Stanford SC (1998a) Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs. Br J Pharmacol 124:1141–1148PubMedCentralPubMed
Zurück zum Zitat Hughes ZA, Stanford SC (1998b) A partial noradrenergic lesion induced by DSP-4 increases extracellular noradrenaline concentration in rat frontal cortex: a microdialysis study in vivo. Psychopharmacology 133:299–303 Hughes ZA, Stanford SC (1998b) A partial noradrenergic lesion induced by DSP-4 increases extracellular noradrenaline concentration in rat frontal cortex: a microdialysis study in vivo. Psychopharmacology 133:299–303
Zurück zum Zitat Hyttel J (1982) Citalopram—pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry 6:277–295PubMed Hyttel J (1982) Citalopram—pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry 6:277–295PubMed
Zurück zum Zitat Jaim-Etcheverry G (1998) 2-Chloroethylamines (DSP4 and xylamine). Toxic action on noradrenergic neurones. In: Kostrzewa RM (ed) Neurotoxins. Basical and clinical applications. Human Press, Iotowa, pp 131–140 Jaim-Etcheverry G (1998) 2-Chloroethylamines (DSP4 and xylamine). Toxic action on noradrenergic neurones. In: Kostrzewa RM (ed) Neurotoxins. Basical and clinical applications. Human Press, Iotowa, pp 131–140
Zurück zum Zitat Jaim-Etcheverry G, Zieher LM (1980) DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523PubMed Jaim-Etcheverry G, Zieher LM (1980) DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523PubMed
Zurück zum Zitat Jaim-Etcheverry G, Zieher LM (1983) 2-Chloroethylamines: new chemical tools for the study of noradrenergic neurons. Trends Pharmacol Sci 4:473–475 Jaim-Etcheverry G, Zieher LM (1983) 2-Chloroethylamines: new chemical tools for the study of noradrenergic neurons. Trends Pharmacol Sci 4:473–475
Zurück zum Zitat Jonsson G (1983) Chemical lesioning techniques: monoamine neurotoxins. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy. Methods in chemical neuroanatomy, vol I. Elsevier, New York, pp 463–507 Jonsson G (1983) Chemical lesioning techniques: monoamine neurotoxins. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy. Methods in chemical neuroanatomy, vol I. Elsevier, New York, pp 463–507
Zurück zum Zitat Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine—a useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72:73–188 Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine—a useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72:73–188
Zurück zum Zitat Jonsson G, Hallman H, Sundström E (1982) Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience 7:2895–2907PubMed Jonsson G, Hallman H, Sundström E (1982) Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience 7:2895–2907PubMed
Zurück zum Zitat Jonsson G, Ross S, Sundström E (1985) Uptake and accumulation of 3H-DSP4, a noradrenaline neurotoxin, in central and peripheral noradrenaline neurons. J Neurochem 44:S184 Jonsson G, Ross S, Sundström E (1985) Uptake and accumulation of 3H-DSP4, a noradrenaline neurotoxin, in central and peripheral noradrenaline neurons. J Neurochem 44:S184
Zurück zum Zitat Kalinin S, Feinstein DL, Hu HL, Huesa G, Pellegrino DA, Galea E (2006) Degeneration of noradrenergic fibers from the locus coeruleus causes tight-junction disorganisation in the rat brain. Eur J Neurosci 24:3393–3400PubMed Kalinin S, Feinstein DL, Hu HL, Huesa G, Pellegrino DA, Galea E (2006) Degeneration of noradrenergic fibers from the locus coeruleus causes tight-junction disorganisation in the rat brain. Eur J Neurosci 24:3393–3400PubMed
Zurück zum Zitat Kalir A, Sabbagh A, Youdim MB (1981) Selective acetylenic ‘suicide’ and reversible inhibitors of monoamine oxidase type A and B. Br J Pharmacol 73:55–64PubMedCentralPubMed Kalir A, Sabbagh A, Youdim MB (1981) Selective acetylenic ‘suicide’ and reversible inhibitors of monoamine oxidase type A and B. Br J Pharmacol 73:55–64PubMedCentralPubMed
Zurück zum Zitat Kammerer RC, Amiri B, Cho AK (1979) Inhibition of uptake of catecholamines by benzylamine derivatives. J Med Chem 22:352–355PubMed Kammerer RC, Amiri B, Cho AK (1979) Inhibition of uptake of catecholamines by benzylamine derivatives. J Med Chem 22:352–355PubMed
Zurück zum Zitat Kask A, Harro J, Tuomaine P, Rägo L, Männistö PT (1997) Overflow of noradrenaline and dopamine in frontal cortex after [N-(2-chloro)-N-ethyl-2-bromobenzylamine] (DSP-4) treatment: in vivo microdialysis study in anaesthetized rats. Naunyn Schmiedebergs Arch Pharmacol 355:267–272PubMed Kask A, Harro J, Tuomaine P, Rägo L, Männistö PT (1997) Overflow of noradrenaline and dopamine in frontal cortex after [N-(2-chloro)-N-ethyl-2-bromobenzylamine] (DSP-4) treatment: in vivo microdialysis study in anaesthetized rats. Naunyn Schmiedebergs Arch Pharmacol 355:267–272PubMed
Zurück zum Zitat Koide M, Cho AK, Howard BD (1986) Characterization of xylamine binding to proteins of PC12 pheochromocytoma cells. J Neurochem 47:1277–1285PubMed Koide M, Cho AK, Howard BD (1986) Characterization of xylamine binding to proteins of PC12 pheochromocytoma cells. J Neurochem 47:1277–1285PubMed
Zurück zum Zitat Korossy-Mruk E, Kuler K, Nowak P, Szkilnik R, Rykaczewska-Czerwinska M, Kostrewa RM, Brus R (2013) Neonatal DSP-4 treatment modifies antinociceptive effects of CB1 receptor agonist methanandamine in adult rats. Neurotox Res 23:39–48PubMedCentralPubMed Korossy-Mruk E, Kuler K, Nowak P, Szkilnik R, Rykaczewska-Czerwinska M, Kostrewa RM, Brus R (2013) Neonatal DSP-4 treatment modifies antinociceptive effects of CB1 receptor agonist methanandamine in adult rats. Neurotox Res 23:39–48PubMedCentralPubMed
Zurück zum Zitat Krueger CA, Cook DA (1975) Synthesis and adrenergic neuron blocking properties of some alkylating analogous of bretylium. Arch Int Pharmacodyn 218:96–105PubMed Krueger CA, Cook DA (1975) Synthesis and adrenergic neuron blocking properties of some alkylating analogous of bretylium. Arch Int Pharmacodyn 218:96–105PubMed
Zurück zum Zitat Landa ME, Rubio MC, Jaim-Etcheverry G (1987) The aziridinium derivative of DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) accelerates the beating rate of isolated atria by enhancing the spontaneous release of noradrenaline. Naunyn Schmiedebergs Arch Pharmacol 336:396–402PubMed Landa ME, Rubio MC, Jaim-Etcheverry G (1987) The aziridinium derivative of DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) accelerates the beating rate of isolated atria by enhancing the spontaneous release of noradrenaline. Naunyn Schmiedebergs Arch Pharmacol 336:396–402PubMed
Zurück zum Zitat Lee CM, Javitch JA, Snyder SH (1982) Characterization of [3H]desipramine binding associated with neuronal norepinephrine uptake in rat brain membranes. J Neurosci 2:1515–1525PubMed Lee CM, Javitch JA, Snyder SH (1982) Characterization of [3H]desipramine binding associated with neuronal norepinephrine uptake in rat brain membranes. J Neurosci 2:1515–1525PubMed
Zurück zum Zitat Lingen B, Brüss M, Bönisch H (1994) Cloning and expression of the bovine sodium- and chloride-dependent noradrenaline transporter. FEBS Lett 342:235–238PubMed Lingen B, Brüss M, Bönisch H (1994) Cloning and expression of the bovine sodium- and chloride-dependent noradrenaline transporter. FEBS Lett 342:235–238PubMed
Zurück zum Zitat Logue MP, Growdon JH, Coviella IL, Wurtman RJ (1985) Differential effects of DSP-4 administration on regional brain norepinephrine turnover in rats. Life Sci 37:403–409PubMed Logue MP, Growdon JH, Coviella IL, Wurtman RJ (1985) Differential effects of DSP-4 administration on regional brain norepinephrine turnover in rats. Life Sci 37:403–409PubMed
Zurück zum Zitat Lyles GA, Callingham BA (1981) The effect of DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] on monoamine oxidase activities in tissues of the rat. J Pharm Pharmacol 33:632–638PubMed Lyles GA, Callingham BA (1981) The effect of DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] on monoamine oxidase activities in tissues of the rat. J Pharm Pharmacol 33:632–638PubMed
Zurück zum Zitat Lynch KS, Ball GF (2008) Noradrenergic deficits after processing of communication signals in female songbirds. Brain Behav Evol 72:207–214PubMed Lynch KS, Ball GF (2008) Noradrenergic deficits after processing of communication signals in female songbirds. Brain Behav Evol 72:207–214PubMed
Zurück zum Zitat Lyons WE, Fritschy JM, Grzanna R (1989) The noradrenergic neurotoxin DSP-4 eliminates the coeruleospinal projection but spares projections of the A5 and A7 groups to the ventral horn of the rat spinal cord. J Neurosci 9:1481–1489PubMed Lyons WE, Fritschy JM, Grzanna R (1989) The noradrenergic neurotoxin DSP-4 eliminates the coeruleospinal projection but spares projections of the A5 and A7 groups to the ventral horn of the rat spinal cord. J Neurosci 9:1481–1489PubMed
Zurück zum Zitat Magyar K, Szende B (2004) (−)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. Neurotoxicology 25:233–242PubMed Magyar K, Szende B (2004) (−)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. Neurotoxicology 25:233–242PubMed
Zurück zum Zitat Mogilnicka E, Dooley DJ, Boissard CG, Delini-Stula A (1983) Altered hind limb extension in the rat after DSP-4: a useful marker of central noradrenergic depletion. Eur J Pharmacol 87:345–347PubMed Mogilnicka E, Dooley DJ, Boissard CG, Delini-Stula A (1983) Altered hind limb extension in the rat after DSP-4: a useful marker of central noradrenergic depletion. Eur J Pharmacol 87:345–347PubMed
Zurück zum Zitat Nowak P, Labus L, Kostrzewa RM, Brus R (2006) DSP-4 prevents dopamine receptor priming by quinpirole. Pharmacol Biochem Behav 84:3–7PubMed Nowak P, Labus L, Kostrzewa RM, Brus R (2006) DSP-4 prevents dopamine receptor priming by quinpirole. Pharmacol Biochem Behav 84:3–7PubMed
Zurück zum Zitat Nowak P, Jochem J, Zwirska-Korczala K, Josko J, Noras L, Kostrzewa RM, Brus R (2008) Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats. Neurotox Res 13:79–83PubMed Nowak P, Jochem J, Zwirska-Korczala K, Josko J, Noras L, Kostrzewa RM, Brus R (2008) Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats. Neurotox Res 13:79–83PubMed
Zurück zum Zitat Nyola A, Kapowich NK, Zhen J, Marden J, Reith ME, Wang DN (2010) Substrate and drug binding sites in LeuT. Curr Opin Struct Biol 20:415–422PubMedCentralPubMed Nyola A, Kapowich NK, Zhen J, Marden J, Reith ME, Wang DN (2010) Substrate and drug binding sites in LeuT. Curr Opin Struct Biol 20:415–422PubMedCentralPubMed
Zurück zum Zitat Olpe HR, Laszio J, Dooley DJ, Heid J, Steinman MW (1983) Decreased activity of locus coeruleus neurons in the rat after DSP-4 treatment. Neurosci Lett 40:81–84PubMed Olpe HR, Laszio J, Dooley DJ, Heid J, Steinman MW (1983) Decreased activity of locus coeruleus neurons in the rat after DSP-4 treatment. Neurosci Lett 40:81–84PubMed
Zurück zum Zitat Palamarchouk VS, Zhang J-J, Zhou G, Schwiergiel AH, Dunn AJ (2000) Hippocampal norepinephrine-like voltammetric responses following infusion of corticotropin-releasing factor into the locus coeruleus. Brain Res Bull 51:319–325PubMed Palamarchouk VS, Zhang J-J, Zhou G, Schwiergiel AH, Dunn AJ (2000) Hippocampal norepinephrine-like voltammetric responses following infusion of corticotropin-releasing factor into the locus coeruleus. Brain Res Bull 51:319–325PubMed
Zurück zum Zitat Paton DM (1973) Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria. Br J Pharmacol 49:614–627PubMedCentralPubMed Paton DM (1973) Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria. Br J Pharmacol 49:614–627PubMedCentralPubMed
Zurück zum Zitat Prieto M, Giralt MT (2001) Effects of N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on alpha2-adrenoceptors which regulate the synthesis and release of noradrenaline in the rat brain. Pharmacol Toxicol 88:152–158PubMed Prieto M, Giralt MT (2001) Effects of N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on alpha2-adrenoceptors which regulate the synthesis and release of noradrenaline in the rat brain. Pharmacol Toxicol 88:152–158PubMed
Zurück zum Zitat Ransom RW, Kammerer RC, Cho AK (1982) Chemical transformations of xylamine (N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine) in solution. Pharmacological activity of the species derived from this irreversible norepinephrine uptake inhibitor. Mol Pharmacol 21:380–386PubMed Ransom RW, Kammerer RC, Cho AK (1982) Chemical transformations of xylamine (N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine) in solution. Pharmacological activity of the species derived from this irreversible norepinephrine uptake inhibitor. Mol Pharmacol 21:380–386PubMed
Zurück zum Zitat Ransom RW, Kammerer RC, Cho AK (1983) The synthesis of [3H]-xylamine, an irreversible inhibitor of norepinephrine uptake. J Label Compounds Radiopharm 20:833–841 Ransom RW, Kammerer RC, Cho AK (1983) The synthesis of [3H]-xylamine, an irreversible inhibitor of norepinephrine uptake. J Label Compounds Radiopharm 20:833–841
Zurück zum Zitat Ransom RW, Waggaman LA, Cho AK (1984) [3H]Xylamine accumulation by two sympathetic innervated tissues. J Neurochem 42:475–481PubMed Ransom RW, Waggaman LA, Cho AK (1984) [3H]Xylamine accumulation by two sympathetic innervated tissues. J Neurochem 42:475–481PubMed
Zurück zum Zitat Ross SB (1976) Long-term effects of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart. Br J Pharmacol 58:521–527PubMedCentralPubMed Ross SB (1976) Long-term effects of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart. Br J Pharmacol 58:521–527PubMedCentralPubMed
Zurück zum Zitat Ross SB, Gosztonyi T (1975) On the mechanism of the accumulation of 3H-bretylium in peripheral sympathomimetic nerves. Naunyn Schmiedebergs Arch Pharmacol 288:233–243 Ross SB, Gosztonyi T (1975) On the mechanism of the accumulation of 3H-bretylium in peripheral sympathomimetic nerves. Naunyn Schmiedebergs Arch Pharmacol 288:233–243
Zurück zum Zitat Ross SB, Rényi AL (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) on the active uptake of noradrenaline. J Pharm Pharmacol 28:458–459PubMed Ross SB, Rényi AL (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) on the active uptake of noradrenaline. J Pharm Pharmacol 28:458–459PubMed
Zurück zum Zitat Ross SB, Johansson JG, Lindborg B, Dahlbom R (1973) Cyclizing compounds. I. Tertiary N-(2-bromobenzyl)-N-haloalkylamines with adrenergic blocking action. Acta Pharm Sueccica 10:29–42 Ross SB, Johansson JG, Lindborg B, Dahlbom R (1973) Cyclizing compounds. I. Tertiary N-(2-bromobenzyl)-N-haloalkylamines with adrenergic blocking action. Acta Pharm Sueccica 10:29–42
Zurück zum Zitat Sanders JD, Happe HK, Bylund DB, Murrin LC (2011) Changes in postnatal norepinephrine alter alpha-2-adrenergic receptor development. Neuroscience 192:761–772PubMedCentralPubMed Sanders JD, Happe HK, Bylund DB, Murrin LC (2011) Changes in postnatal norepinephrine alter alpha-2-adrenergic receptor development. Neuroscience 192:761–772PubMedCentralPubMed
Zurück zum Zitat Schuerger RJ, Balaban CD (1995) N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has differential efficacy for causing central noradrenergic lesions in two different rat strains: comparison between Long-Evans and Sprague-Dawley rats. J Neurosci Methods 58:95–101PubMed Schuerger RJ, Balaban CD (1995) N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has differential efficacy for causing central noradrenergic lesions in two different rat strains: comparison between Long-Evans and Sprague-Dawley rats. J Neurosci Methods 58:95–101PubMed
Zurück zum Zitat Szökö E, Haberle D, Halász AS, Tekes K, Magyar K (2001) Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus. J Neural Transm 108:407–413PubMed Szökö E, Haberle D, Halász AS, Tekes K, Magyar K (2001) Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus. J Neural Transm 108:407–413PubMed
Zurück zum Zitat Szot P, Miguelez C, White SS, Franklin A, Sikkema C, Wilkinson CW, Ugedo L, Rasking MA (2010) A comprehensive analysis of the effect of DSP4 on the locus coeruleus noradrenergic system in the rat. Neuroscience 166:279–291PubMedCentralPubMed Szot P, Miguelez C, White SS, Franklin A, Sikkema C, Wilkinson CW, Ugedo L, Rasking MA (2010) A comprehensive analysis of the effect of DSP4 on the locus coeruleus noradrenergic system in the rat. Neuroscience 166:279–291PubMedCentralPubMed
Zurück zum Zitat Tejani-Butt SM (1992) [3H]nisoxetine: a radioligand for quantitation of norepinephrine uptake sites by autoradiography or by homogenate binding. J Pharmacol Exp Ther 260:427–436PubMed Tejani-Butt SM (1992) [3H]nisoxetine: a radioligand for quantitation of norepinephrine uptake sites by autoradiography or by homogenate binding. J Pharmacol Exp Ther 260:427–436PubMed
Zurück zum Zitat Vahaba DM, Lacey WH, Tomaszycki MI (2013) DSP-4, a noradrenergic neurotoxin, produced sex-specific effects on pairing and courtship behavior in zebra finches. Behav Brain Res 252:164–175PubMed Vahaba DM, Lacey WH, Tomaszycki MI (2013) DSP-4, a noradrenergic neurotoxin, produced sex-specific effects on pairing and courtship behavior in zebra finches. Behav Brain Res 252:164–175PubMed
Zurück zum Zitat Villani L, Guarnieri E, Facchinetti F, Virgili M, Poli A (1996) Neurotoxic effects of DSP-4 on the noradrenergic system of the goldfish brain. Brain Behav Evol 47:219–224PubMed Villani L, Guarnieri E, Facchinetti F, Virgili M, Poli A (1996) Neurotoxic effects of DSP-4 on the noradrenergic system of the goldfish brain. Brain Behav Evol 47:219–224PubMed
Zurück zum Zitat Wang Y, Musich PR, Serrano MA, Zou Y, Zhang J, Zhu MY (2014) Effects of DSP4 on the noradrenergic phenotypes and its potential molecular mechanisms in SH-SYS5Y cells. Neurotox Res 25:193–207PubMed Wang Y, Musich PR, Serrano MA, Zou Y, Zhang J, Zhu MY (2014) Effects of DSP4 on the noradrenergic phenotypes and its potential molecular mechanisms in SH-SYS5Y cells. Neurotox Res 25:193–207PubMed
Zurück zum Zitat Waterman SA, Harding CF (2008) Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches. Behav Brain Res 188:271–280PubMedCentralPubMed Waterman SA, Harding CF (2008) Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches. Behav Brain Res 188:271–280PubMedCentralPubMed
Zurück zum Zitat Weinreb O, Amit T, Riederer P, Youdim MB, Mandel SA (2011) Neuroprotective profile of the multitarget drug rasagiline in Parkinson’s disease. Int Rev Neurobiol 100:127–149PubMed Weinreb O, Amit T, Riederer P, Youdim MB, Mandel SA (2011) Neuroprotective profile of the multitarget drug rasagiline in Parkinson’s disease. Int Rev Neurobiol 100:127–149PubMed
Zurück zum Zitat Wenge B, Bönisch H (2009) Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters. Naunyn Schmiedebergs Arch Pharmacol 380:523–529PubMed Wenge B, Bönisch H (2009) Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters. Naunyn Schmiedebergs Arch Pharmacol 380:523–529PubMed
Zurück zum Zitat Wenge B, Bönisch H (2013) The role of cysteines and histidines of the norepinephrine transporter. Neurochem Res 58:1303–1314 Wenge B, Bönisch H (2013) The role of cysteines and histidines of the norepinephrine transporter. Neurochem Res 58:1303–1314
Zurück zum Zitat Wolfman C, Abó V, Calvo D, Medina J, Dajas F, Silveira R (1994) Recovery of central noradrenergic neurons one year after the administration of the neurotoxin DSP4. Neurochem Int 25:395–400PubMed Wolfman C, Abó V, Calvo D, Medina J, Dajas F, Silveira R (1994) Recovery of central noradrenergic neurons one year after the administration of the neurotoxin DSP4. Neurochem Int 25:395–400PubMed
Zurück zum Zitat Yu PH, Davis BA, Fang J, Boulton AA (1994) Neuroprotective effects of some monoamine oxidase-B inhibitors against DSP-4-induced noradrenaline depletion in the mouse hippocampus. J Neurochem 63:1820–1828PubMed Yu PH, Davis BA, Fang J, Boulton AA (1994) Neuroprotective effects of some monoamine oxidase-B inhibitors against DSP-4-induced noradrenaline depletion in the mouse hippocampus. J Neurochem 63:1820–1828PubMed
Zurück zum Zitat Yu PH, Davis BA, Zhang X, Zuo DM, Fang J, Lai CT, Li XM, Paterson IA, Boulton AA (1995) Neurochemical, neuroprotective and neurorescue effects of aliphatic N-propargylamines; new MAO-B inhibitors without amphetamine-like properties. Prog Brain Res 106:113–121PubMed Yu PH, Davis BA, Zhang X, Zuo DM, Fang J, Lai CT, Li XM, Paterson IA, Boulton AA (1995) Neurochemical, neuroprotective and neurorescue effects of aliphatic N-propargylamines; new MAO-B inhibitors without amphetamine-like properties. Prog Brain Res 106:113–121PubMed
Zurück zum Zitat Yu PH, Zhang X, Zuo DM, Lai CT, Tieu K, Davis BA, Boulton AA (1998) Aliphatic N-methylpropargylamines as potential neurorescue agents. Restor Neurol Neurosci 12:113–118PubMed Yu PH, Zhang X, Zuo DM, Lai CT, Tieu K, Davis BA, Boulton AA (1998) Aliphatic N-methylpropargylamines as potential neurorescue agents. Restor Neurol Neurosci 12:113–118PubMed
Zurück zum Zitat Zaczek R, Fritschy JM, Culp S, De Souza EB, Grzanna R (1990) Differential effects of DSP-4 on noradrenaline axons in cerebral cortex and hypothalamus may reflect heterogeneity of noradrenaline uptake sites. Brain Res 522:308–314PubMed Zaczek R, Fritschy JM, Culp S, De Souza EB, Grzanna R (1990) Differential effects of DSP-4 on noradrenaline axons in cerebral cortex and hypothalamus may reflect heterogeneity of noradrenaline uptake sites. Brain Res 522:308–314PubMed
Zurück zum Zitat Zhang X, Yu PH (1995) Depletion of NOS activity in the rat dentate gyrus neurons by DSP-4 and protection by deprenyl. Brain Res Bull 38:307–311PubMed Zhang X, Yu PH (1995) Depletion of NOS activity in the rat dentate gyrus neurons by DSP-4 and protection by deprenyl. Brain Res Bull 38:307–311PubMed
Zurück zum Zitat Zhang X, Zuo DM, Yu PH (1995) Neuroprotection by R(−)-deprenyl and N-(2-hexyl-N-methylpropargylamine on DSP-4, a neurotoxin. Induced degeneration of noradrenergic neurons in the rat locus coeruleus. Neurosci Lett 186:45–48PubMed Zhang X, Zuo DM, Yu PH (1995) Neuroprotection by R(−)-deprenyl and N-(2-hexyl-N-methylpropargylamine on DSP-4, a neurotoxin. Induced degeneration of noradrenergic neurons in the rat locus coeruleus. Neurosci Lett 186:45–48PubMed
Zurück zum Zitat Zhang X, Zuo DM, Davis BA, Boulton AA, Yu PH (1996) Immunohistochemical evidence of neuroprotection by R(−)-deprenyl and N-(2-hexyl-N-methylpropargylamine on DSP-4-induced degeneration of rat brain noradrenergic axons and terminals. J Neurosci Res 43:482–489PubMed Zhang X, Zuo DM, Davis BA, Boulton AA, Yu PH (1996) Immunohistochemical evidence of neuroprotection by R(−)-deprenyl and N-(2-hexyl-N-methylpropargylamine on DSP-4-induced degeneration of rat brain noradrenergic axons and terminals. J Neurosci Res 43:482–489PubMed
Zurück zum Zitat Zhang J-J, Schwiergiel AH, Palamarchouk VS, Dunn AJ (1998) Intraventricular infusion of CRF increases extracellular concentrations of norepinephrine in the hippocampus and cortex as determined by in vivo voltammetry. Brain Res Bull 47:277–284PubMed Zhang J-J, Schwiergiel AH, Palamarchouk VS, Dunn AJ (1998) Intraventricular infusion of CRF increases extracellular concentrations of norepinephrine in the hippocampus and cortex as determined by in vivo voltammetry. Brain Res Bull 47:277–284PubMed
Zurück zum Zitat Zieher LM, Jaim-Etcheverry G (1980) Neurotoxicity of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) on noradrenergic neurons is mimicked by its cyclic aziridinium derivative. Eur J Pharmacol 65:249–256PubMed Zieher LM, Jaim-Etcheverry G (1980) Neurotoxicity of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) on noradrenergic neurons is mimicked by its cyclic aziridinium derivative. Eur J Pharmacol 65:249–256PubMed
Metadaten
Titel
DSP4, a Selective Neurotoxin for the Locus Coeruleus Noradrenergic System. A Review of Its Mode of Action
verfasst von
Svante B. Ross
Carina Stenfors
Publikationsdatum
01.01.2015
Verlag
Springer US
Erschienen in
Neurotoxicity Research / Ausgabe 1/2015
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI
https://doi.org/10.1007/s12640-014-9482-z

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