MODULATION OF THE INHIBITORY EFFECT OF PHENYLETHYLAMINE ON SPONTANEOUS MOTOR-ACTIVITY IN MICE BY CPP-(+ -)-3-(2-CARBOXYPIPERAZIN-4-YL)-PROPYL-1-PHOSPHONIC ACID/

beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous motor activity in mice. -)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosph onic acid, a selective and competitive antagonist of N-methyl-D-aspart ate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antago nizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pre treament with noncompetitive antagonists of NMDA receptors, such as di zocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperi dol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagoniz e the inhibitory effect of other tested drugs such as diazepam, halope ridol, baclofen and phenibut. Intracerebroventricularly administered N MDA (0.2 mu M), an agonist of NMDA receptors, suppressed the antagonis tic 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 syner gism 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 effec ts on PEA-induced inhibition of locomotion. This effect was not associ ated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 mu M) or l ow (4.3 mu M) concentration of PEA as a substrate in the medium. Mecha nism of the interaction of CPP and PEA, two drugs belonging to differe nt groups of biologically active compounds, deserves further studies. Copyright (C) 1997 Elsevier Science Inc.