The antiparkinsonian drugs budipine and biperiden are use-dependent (uncompetitive) NMDA receptor antagonists.
N-Methyl-D-aspartate- (NMDA-) evoked [3H]acetylcholine release in rabbit caudate nucleus slices was inhibited by the antiparkinsonian drugs budipine (1-tert-butyl-4,4-diphenylpiperidine) and biperiden (1-bicyclo[2.2.1.]hept-5-en-2-yl-1-phenyl-3-piperidino propanol) yielding functional Ki values of 4.6 and 8.8 microM. In contrast to the competitive antagonist 2-amino-5-phosphonopentaonate, budipine and biperidene significantly reduced both the apparent KD and the Emax value of NMDA. Moreover, they displaced [3H]MK-801 specifically bound to membranes of the same tissue, although with low affinity (IC50: 38 and 92 microM). It is concluded that budipine and biperiden are use-dependent (uncompetitive) antagonists at the NMDA receptor, binding to the receptor-linked ion channel, but probably not to the MK-801 binding site. NMDA antagonism may contribute to the antiparkinsonian effects of budipine.
Pharmakologisches Institut der Universität, Freiburg, Germany.
R
R
Jackisch
A
A
Kruchen
W
W
Sauermann
G
G
Hertting
T J
TJ
Feuerstein
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001712:Biperiden / Q000378:metabolism / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D066298:In Vitro Techniques; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012984:Software
D000978:Antiparkinson Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D001712:Biperiden; D016291:Dizocilpine Maleate; C026710:budipine; D000109:Acetylcholine