Summary
The ability of systemically and locally administered prazosin to block α1-adrenoceptors was examined in two brain areas in the rat. Using single unit recording of neurons in the lateral geniculate and dorsal raphe nuclei, evidence was obtained for the selective blockade of α1-adrenoceptors by both intravenous and iontophoretic prazosin. Since effective systemic doses of prazosin were within the clinical range, it appears likely that brain α1-adrenoceptors would be blocked during prazosin therapy in humans.
References
Anden N-E, Gomes C, Persson B, Trolin G (1978) R 28935 and prazosin: effects on central and peripheral alpha-adrenoceptor activity and on blood pressure. Naunyn-Schmiedeberg's Arch Pharmacol 302:299–306
Baraban JM, Aghajanian GK (1980) Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists. Neuropharmacology 19:355–363
Baraban JM, Wang RY, Aghajanian GK (1978) Reserpine suppression of dorsal raphe neuronal firing: mediation by adrenergic system. Eur J Pharmacol 52:27–36
Cavero I, Roach AG (1980) The pharmacology of prazosin, a novel antihypertensive agent. Life Sci 27:1525–1540
Graham RM, Pettinger WA (1979) Drug Therapy: Prazosin. New England J Med 300:232–236
Greengrass P, Bremner R (1979) Binding characteristics of 3H-prazosin to rat brain α-adrenergic receptors. Eur J Pharmacol 55:323–326
Haigler HJ, Aghajanian GK (1974) Lysergic aicd diethylamide and serotonin: a comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. J Pharmacol Exp Therapeut 188:688–699
Hornung R, Presek P, Glossmann H (1979) Alpha adrenoceptors in rat brain: direct identification with prazosin. Naunyn-Schmiedeberg's Arch Pharmacol 308:223–230
Karlberg BE, Thulin T, Fagerberg SE, Schersten B, Tolagen K, Vikesdal O, Malmberg L (1979) Effects of prazosin on plasma renin activity and blood pressure. J Clin Pharmacol 19:357–365
Langer SZ, Cavero I, Massingham R (1980) Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. Hypertension 2:372–382
Marwaha J, Aghajanian GK (1981) Relative potencies of antagonists at α2-adrenoceptors of the locus coeruleus and α1-adrenoceptors of the lateral geniculate nucleus. Soc Neurosci Abstr 7: (in press)
McCall RB, Humphrey SJ (1981) Evidence for a central depressor action of postsynaptic α1-adrenergic receptor antagonists. J Autonom Nerv Sys 3:9–24
Miach PJ, Dausse JP, Cardot A, Meyer P (1980) 3H-prazosin binds specifically to α1-adrenoceptors in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 312:23–26
Roach AG, Gomeni R, Mitchard M, Nicolas JP, Cavero I (1978) The blood pressure lowering effects of intravenous versus intracerebroventricular prazosin in anesthetized cats. Eur J Pharmacol 49: 271–278
Rogawski MA, Aghajanian GK (1980) Activation of lateral geniculate neurons by norepinephrine: mediation by an α-adrenergic receptor. Brain Res 182:345–359
Rogawski MA, Aghajanian GK (1981) Activation of lateral geniculate neurons by noradrenergic pathway stimulation: selective blockade by the α1-adrenoceptors antagonist prazosin. Soc Neurosci Abstr 7: (in press)
Taylor JA, Twomey TM, Schach VonWittenau M (1977) The metabolic fate of prazosin. Xenobiotica 7:357–364
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Menkes, D.B., Baraban, J.M. & Aghajanian, G.K. Prazosin selectively antagonizes neuronal responses mediated by α1-adrenoceptors in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 317, 273–275 (1981). https://doi.org/10.1007/BF00503830
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00503830