Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity.

摘要: SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H-benzo[d]naptho-(2,1-b)azepine] is a benzonaphthazepine that has been evaluated as selective D1 dopamine receptor antagonist. In vitro, (Ki = 3.6 nM) inhibited the binding of [3H]SCH23390 (a specific compound) and blocked dopamine-stimulated adenylate cyclase 9.1 nM); in contrast Ki for to displace [3H]spiperone (D2) was greater than 1 microM its vs. [3H]-ketanserin (5-hydroxytryptamine2) 300 nM. vivo, both rat squirrel monkey conditioned avoidance responding (minimal effective dose 10 1.78 mg/kg p.o., respectively) had duration at least 6 hr species. addition, antagonized apomorphine-induced stereotypy rats p.o.). These vivo actions are similar activity typical antagonists. However, D2-selective antagonists, failed increase plasma prolactin levels, did not block emesis dog minimal effects on striatal levels homovanillic acid or dihydroxyphenylacetic acid. Furthermore, although immobility seen after p.o. administration using inclined screen test, drug cause catalepsy doses up times response test. Additionally, climbing lower it sniffing mice. The results from these latter two tests suggest may have reduced liability produce extrapyramidal side effects. Therefore, based this profile activity, antagonist vitro vivo. because compound longer acting primate previously available potential utility clinically useful drug.