Yu. Yu. Firstova1, D. A. Abaimov, I. G. Kapitsa, T. A. Voronina, and G. I. Kovalev
Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia
Received September 6, 2010
Abstract—We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoyl-
methyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA),
serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the
conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia
ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (Bmax)
of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippoc-
ampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of
scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phe-
notropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1receptors.
Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil
increased the density of receptors by 16% and 25%, respectively. Phenotropil considerably increased the den-
sity of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density
of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics
of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results dem-
onstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical
mechanisms of the anti-amnestic effects of phenotropil.
Keywords: phenotropil, nootropic drugs, scopolamine, PAT, dopamine, serotonin, acetylcholine, glutamate,
benzodiazepines, striatum, frontral cortex, hippocampus
DOI: 10.1134/S1819712411020048
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