Evidence that Ginkgo biloba extract does not inhibit MAO A and B in living human brain

doi:10.1016/S0024-3205(99)00660-8

Life Sciences

Volume 66, Issue 9, 21 January 2000, Pages PL141-PL146

https://doi.org/10.1016/S0024-3205(99)00660-8 Get rights and content

Abstract

Extracts of Ginkgo biloba have been reported to reversibly inhibit both monoamine oxidase (MAO) A and B in rat brain in vitro leading to speculation that MAO inhibition may contribute to some of its central nervous system effects. Here we have used positron emission tomography (PET) to measure the effects of Ginkgo biloba on human brain MAO A and B in 10 subjects treated for 1 month with 120 mg/day of the Ginkgo biloba extract EGb 761, using [¹¹C]clorgyline and [¹¹C]L-deprenyl-D2 to measure MAO A and B respectively. A three-compartment model was used to calculate the plasma to brain transfer constant K₁, which is related to blood flow, and λk₃, a model term which is a function of the concentration of catalytically active MAO molecules. Ginkgo biloba administration did not produce significant changes in brain MAO A or MAO B suggesting that mechanisms other than MAO inhibition need to be considered as mediating some of its CNS effects.

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In order to explain cognition-enhancing effects of standardized Ginkgo biloba extract (EGb761^®), an increase of central monoaminergic neurotransmission has been suggested, but the underlying mechanisms have not yet been elucidated. Here, we confirm that the norepinephrine (NET), the serotonin (SERT), the dopamine (DAT) uptake transporters and MAO activity are inhibited by EGb761^® in vitro, although rather high concentrations are required for inhibition of MAO-A and MAO-B activity. However, after 14 days of daily oral treatment with 100 mg/kg EGb761^® only NE uptake is significantly decreased in NMRI mice, while 5-HT uptake and MAO activity are not affected. As synaptic dopamine clearance in the frontal cortex is mediated by NET, not DAT, these findings may give an explanation for the enhancement of dopaminergic neurotransmission by EGb761^® seen in animal models, presumably linked to its positive effects on cognition and attention.
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Pharmacology letter accelerated communicationEvidence that Ginkgo biloba extract does not inhibit MAO A and B in living human brain

Abstract

The Lancet

Jpn J Pharmacol

Life Sciences

Gen. Pharmac

Life Sci

Tetrahedron

Biochem Pharmacol

Nucl. Med. Biol.

JAMA

Arch Int Med

N Eng J Med

J Neural Transm Suppl

Pharmacology letter accelerated communication
Evidence that Ginkgo biloba extract does not inhibit MAO A and B in living human brain