Pharmacological evaluation of HP 370, a potential atypical antipsychotic agent: 2. In vitro profile
作者:
Francis P. Huger,
Craig P. Smith,
Yulin Chiang,
Edward J. Glamkowski,
Daniel B. Ellis,
期刊:
Drug Development Research
(WILEY Available online 1987)
卷期:
Volume 11,
issue 3‐4
页码: 169-175
ISSN:0272-4391
年代: 1987
DOI:10.1002/ddr.430110304
出版商: Wiley Subscription Services, Inc., A Wiley Company
关键词: neurotransmitter receptor binding;uptake;neuroleptic;clozapine
数据来源: WILEY
摘要:
AbstractHP 370, 4,9‐dibromo‐6‐(4‐methyl‐1‐piperazinyl)benzo[b]pyrrolo[3,2,1‐jk][1,4] benzodiazepine, a compound that has an atypical antipsychotic profile in vivo, was tested for activity in a number of neurotransmitter receptor binding and uptake assays and compared with serveral typical and atypical antipsychotic compounds. The in vitro profile of HP 370 was most similar to that of clozapine, with the notable exception that HP 370 was inactive as an inhibitor of quinuclidinyl benzilate (QNB) binding (IC5010−5). HP 370, like clozapine, was a relatively weak and nonselective inhibitor of dopamine (DA) receptor subtypes, whereas sulpiride, another compound reported to be atypical, is a very selective but weak inhibitor of dopamine‐2(D2) receptors. HP 370 and clozapine inhihited WB4101 binding with high affinity, indicating α1‐adrenergic receptor blockade. Neither HP 370 nor the standard neuroleptic compounds inhibited flunitrazepam or gamma‐aminobutyric acid (GABA) binding. HP 370, Clozapine, and sulpiride were inactive as inhibitors of norepinephrine (NE), DA, and 5HT uptake, whereas HP 370 AND clozapine were weark inhibitors of GABA uptake. Based on this in vitro data, the mesolimbic site‐selectivity of HP 370 seen in vivo cannot be explained by anticholinergic GABA‐mimetic activity in the DA‐parative results point to a distinct advantage of an atypical neuroleptic, without the antocholinerg
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