The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist.
Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 microM suggesting that budopine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).
Klockgether
T
T
Department of Neurology, University of Tübingen, Federal Republic of Germany.
Jacobsen
P
P
Löschmann
P A
PA
Turski
L
L
D000596:Amino Acids / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D006181:H-Reflex / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012023:Reflex, Monosynaptic / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013116:Spinal Cord / Q000187:drug effects
D000596:Amino Acids; D000978:Antiparkinson Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C012058:tenocyclidine; D010622:Phencyclidine; C026710:budipine