Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor

An amnesic effect of anticholinergic drugs was previously described from se veral behavioral studies. We examined this effect induced by trihexyphenidy l and biperiden, clinically used in the parkinsonism and schizophrenic pati ents, by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, s.c.) showed dose-dependent amnesic effects in the acquisition and retrieva l phases. However, the effect induced by trihexyphenidyl was transient, whe reas that of biperiden was long-lasting. To clarify the reason for the diff erent duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [H-3 ]quinuclidinyl benzilate ([H-3]QNB) on the muscarinic receptor (showed incr eased K-d and unchanged B-max value), while biperiden decreased [H-3]QNB bi nding (B-max value) significantly. Furthermore, in an exchange assay for re ceptor inactivation, trihexyphenidyl binding to muscarinic receptors was ex changed by [H-3]QNB completely, but biperiden decreased the exchangeable bi nding of [H-3]QNB in a dose dependent manner (0.1-100 nM). These results su ggested that the binding of trihexyphenidyl and biperiden to muscarinic rec eptor might be completely reversible and partially irreversible, respective ly, whereas the Ki values of these two drugs were similar. In conclusion, t his difference in binding property may explain the difference in the time-c ourse of the amnesic effect induced by trihexyphenidyl and biperiden. (C) 1 999 Elsevier Science B.V. All rights reserved.