Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum.
Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D2 receptor density in the striatum was investigated after a drug-free period of five days. The D2 receptor system as analysed by [3H]-spiperone binding was best characterized by a model with two binding sites of different affinity and the following constants: KDhigh = 0.13 nmol/l; KDlow = 5.8 nmol/l; Bmax high = 107 fmol/mg prot.; Bmax low = 598 fmol/mg prot. Chronic haloperidol treatment substantially augmented the total binding capacity primarily, if not exclusively, due to an increase of Bmax low. 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.
D000818:Animals; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D006220:Haloperidol / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology
D002090:Butyrophenones; D013134:Spiperone; D013792:Thalidomide; D006220:Haloperidol; C027948:supidimide; D003975:Diazepam; D010634:Phenobarbital