Study of beta-adrenoreceptor antagonistic activity of DPJ 904 in rats.
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.
Nandakumar
K
K
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, India.
Bansal
S K
SK
Singh
Randhir
R
Mohite
A J
AJ
Bodhankar
S L
SL
Jindal
D P
DP
Coumar
Mohane S
MS
Balaraman
R
R
Bhardwaj
S H
SH
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
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; C503288:DPJ 904; D010091:Oximes; D007545:Isoproterenol