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  • Title: Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum.
    Author: Hennies HH, Hess V, Flohé L.
    Journal: Arzneimittelforschung; 1984; 34(11):1481-4. PubMed ID: 6543122.
    Abstract:
    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.
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