R. Jackisch et al., THE ANTIPARKINSONIAN DRUGS BUDIPINE AND BIPERIDEN ARE USE-DEPENDENT (UNCOMPETITIVE) NMDA RECEPTOR ANTAGONISTS, European journal of pharmacology, 264(2), 1994, pp. 207-211
N-Methyl-D-aspartate- (NMDA-) evoked [H-3]acetylcholine release in rab
bit caudate nucleus slices was inhibited by the antiparkinsonian drugs
budipine (1-tert-butyl-4,4-diphenylpiperidine) and biperiden icyclo[2
.2.1.]hept-5-en-2-yl-1-phenyl-3-piperidino propanol) yielding function
al K-i values of 4.6 and 8.8 mu M. In contrast to the competitive anta
gonist 2-amino-5-phosphonopentaonate, budipine and biperidene signific
antly reduced both the apparent K-D and the E(max) value of NMDA. More
over, they displaced [H-3]MK-801 specifically bound to membranes of th
e same tissue, although with low affinity (IC50: 38 and 92 mu M). It i
s concluded that budipine and biperiden are use-dependent (uncompetiti
ve) antagonists at the NMDA receptor, binding to the receptor-linked i
on channel, but probably not to the MK-801 binding site. NMDA antagoni
sm may contribute to the antiparkinsonian effects of budipine.