Effects of Chronic Chlorpromazine Treatment on Peripheral Benzodiazepine Binding Sites in Heart, Kidney, and Cerebral Cortex of Rats

Abstract

Daily intraperitoneal administration to rats of 5 mg/kg of chlorpromazine (CPZ) for 21 days induced a significant up-regulation (51%) of peripheral benzodiazepine binding sites (PBSs) in cerebral cortex and a down-regulation of PBSs in the heart (25%) and kidney (14%), whereas no alteration in [3H]flunitrazepam binding in cerebral cortex was observed. [3H]PK 11195 binding to cerebral cortex returned to normal following 5 days of CPZ withdrawal, whereas the density of PBSs in the heart and kidney remained reduced. The affinity of PBSs for the ligand [3H]PK 11195 in the cerebral cortex and heart was not affected by the drug treatment or withdrawal. The CPZ-induced alterations in PBSs may be relevant to the effects of the drug on CNS and/or peripheral organs.

Decreases in peripheral-type benzodiazepine receptors in postmortem brains of chronic schizophrenics

“…The reduction in Bmax in the superior parietal cortex and the decrease in Kd in the primary visual area were also marked in the off-drug cases of the schizophrenics, while the decrease in Kd in the superior parietal cortex was statistically significant in the on-drug cases. In rat brains, chronic treatment with antipsychotic drugs, such as haloperidol and chlorpromazine, produced an increase in Bmax of [3H] PK 11195 binding, but not Kd, in the olfactory bulb (Kurumaji et al, 1996b) and in the cerebral cortex (Gavish et al, 1988;Gavish and Weizman, 1989). Thus, it is unlikely that medication with antipsychotic drugs produced the decreases in Bmax and Kd of [3H] PK 11195 binding in the schizophrenic brains.…”