title: CGS 7525A, a new, centrally active alpha 2 adrenoceptor antagonist.
abstract: CGS 7525A, a new tetracyclic compound, was evaluated for alpha 2 adrenoceptor antagonism in receptor binding assays and in behavioral and electrophysiological tests. 3H-Clonidine, but not 3H-prazosin, binding was potently inhibited in vitro by CGS 7525A. In vivo, CGS 7525A attenuated the suppressant action of clonidine on phenylquinone-induced writhing and on locus coeruleus neuronal firing rate. Mianserin was nearly equipotent with CGS 7525A in the 3H-clonidine binding assay, but considerably less potent in the measures of alpha 2 adrenoceptor antagonism in vivo. Both CGS 7525A and mianserin displaced 3H-spiroperidol binding from frontal cortex 5-HT2 binding sites. Although yohimbine resembled CGS 7525A in most respects, its activity at 5-HT2 binding sites was relatively low, CGS 7525A was not associated with any appreciable blockade of norepinephrine or serotonin uptake in vitro. Thus, CGS 7525A appears to be a promising new pharmacological tool for investigating the behavioral function of brain alpha 2 adrenoceptors.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects; D008803:Mianserin / Q000378:metabolism / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D011809:Quinones; D001569:Benzodiazepines; C037604:aptazapine; D008803:Mianserin; D015016:Yohimbine; D013134:Spiperone; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin