title: Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-carboxypiperazin-4-YL)-propyl-1-phosphonic acid.
abstract: Beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous, motor activity in mice. CPP- (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 microM), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg) an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 microM) or low (4.3 microM) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies.
authors.affiliation: Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: I P
authors.initials: IP
authors.lastname: Lapin
authors.forename: A
authors.initials: A
authors.lastname: Yuwiler
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D010627:Phenethylamines / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010879:Piperazines; D012642:Selegiline; C029261:phenethylamine; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008995:Monoamine Oxidase