title: Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum.
abstract: Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.
authors.affiliation: Department of Neurology, Medical Faculty, Free University, Amsterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Drukarch
authors.forename: E
authors.initials: E
authors.lastname: Schepens
authors.forename: M J
authors.initials: MJ
authors.lastname: Dolleman-Van der Weel
authors.forename: P
authors.initials: P
authors.lastname: De Boer
authors.forename: B J
authors.initials: BJ
authors.lastname: Van Vliet
authors.forename: J C
authors.initials: JC
authors.lastname: Stoof
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D016627:Oxidopamine; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013563:Sympathectomy, Chemical
chemical_list: D001381:Azepines; D015259:Dopamine Agents; D004873:Ergolines; D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D005576:Colforsin; D019257:Quinpirole; C024763:talipexole; D016627:Oxidopamine; D000262:Adenylyl Cyclases