title: Study of beta-adrenoreceptor antagonistic activity of DPJ 904 in rats.
abstract: beta-Adrenoreceptor antagonistic activity of a newly synthesized compound was evaluated in vivo by measuring the mean arterial blood pressure and heart rate of urethane-anesthetized rats treated with isoprenaline. In vitro beta(1)-, beta(2)- and beta(3)-antagonism was studied using isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively, in comparison to isoprenaline response. DPJ 904 (1, 3 and 10 mg/kg, i.v.) produced dose-dependent hypotensive and bradycardia response in anesthetized rat. DPJ 904 (1, 3 and 10 mg/kg, i.v.) significantly inhibited both the tachycardial effects and hypotensive response induced by isoprenaline. DPJ 904-antagonized isoprenaline induced positive chronotropic effects of isolated rat right atria and a uterine relaxant effect indicating beta(1)- and beta(2)-blockade. The parallel shift to the right of the concentration-response curve of isoprenaline in the presence of DPJ 904 in KCl (30 mmol/l) induced contraction of the rat colon suggesting that DPJ 904 also possessed beta(3)-adrenoreceptor antagonistic activity. The selectivity to beta(1)-adrenoreceptor was nearly 20.5 times greater than to beta(2)-adrenoreceptor. The present study indicates that DPJ 904 possesses beta-adrenoreceptor antagonistic activity with slightly more affinity to the beta(1)-adrenoreceptor subtype.
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, India.
authors.forename: K
authors.initials: K
authors.lastname: Nandakumar
authors.forename: S K
authors.initials: SK
authors.lastname: Bansal
authors.forename: Randhir
authors.initials: R
authors.lastname: Singh
authors.forename: A J
authors.initials: AJ
authors.lastname: Mohite
authors.forename: S L
authors.initials: SL
authors.lastname: Bodhankar
authors.forename: D P
authors.initials: DP
authors.lastname: Jindal
authors.forename: Mohane S
authors.initials: MS
authors.lastname: Coumar
authors.forename: R
authors.initials: R
authors.lastname: Balaraman
authors.forename: S H
authors.initials: SH
authors.lastname: Bhardwaj
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; C503288:DPJ 904; D010091:Oximes; D007545:Isoproterenol