Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor
Brain Research, ISSN: 0006-8993, Vol: 834, Issue: 1, Page: 6-12
1999
- 25Citations
- 30Captures
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Metrics Details
- Citations25
- Citation Indexes25
- 25
- CrossRef19
- Captures30
- Readers30
- 30
Article Description
An amnesic effect of anticholinergic drugs was previously described from several behavioral studies. We examined this effect induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, 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 retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [ 3H ]quinuclidinyl benzilate ([ 3H ]QNB) on the muscarinic receptor (showed increased K d and unchanged B max value), while biperiden decreased [ 3H ]QNB binding ( B max value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [ 3H ]QNB completely, but biperiden decreased the exchangeable binding of [ 3H ]QNB in a dose dependent manner (0.1–100 nM). These results suggested that the binding of trihexyphenidyl and biperiden to muscarinic receptor might be completely reversible and partially irreversible, respectively, whereas the K i values of these two drugs were similar. In conclusion, this difference in binding property may explain the difference in the time-course of the amnesic effect induced by trihexyphenidyl and biperiden.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0006899399015267; http://dx.doi.org/10.1016/s0006-8993(99)01526-7; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0033542804&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/10407088; https://linkinghub.elsevier.com/retrieve/pii/S0006899399015267; http://linkinghub.elsevier.com/retrieve/pii/S0006899399015267; http://api.elsevier.com/content/article/PII:S0006899399015267?httpAccept=text/xml; http://api.elsevier.com/content/article/PII:S0006899399015267?httpAccept=text/plain; http://dx.doi.org/10.1016/s0006-8993%2899%2901526-7; https://dx.doi.org/10.1016/s0006-8993%2899%2901526-7
Elsevier BV
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