Method for assessing the activity of drugs at beta 1- and beta 2-adrenoceptors in the same animal.
A method is described for assessing the selectivity of compounds for beta 1- and beta 2-adrenoceptors in vivo. The potency of selective beta-adrenoceptor agonists to increase heart rate and decrease uterine contractions in pithed rats and in isolated tissues was determined. The order of potency both in vivo (i.v. route) and in vitro was: isoprenaline greater than noradrenaline greater than salbutamol on heart rate, and isoprenaline greater than salbutamol greater than noradrenaline on uterine relaxation. Fenoterol, salbutamol, and BRL 26830A/28410, but not denopamine, (i.p.) route were more potent stimulants of uterine relaxation than of heart rate in pithed rats and in vitro. The abilities of atenolol (beta 1-selective), ICI 118551 (beta 2-selective) and propranolol (non selective between beta 1- and beta 2-adrenoceptors) to inhibit responses to isoprenaline on heart rate and uterine contractions in vivo were also assessed. The effects of isoprenaline on heart rate were selectively antagonized by atenolol while those on the uterus were selectively antagonized by ICI 118551. These results show that beta 1-adrenoceptors mediate increases in heart rate and that beta 2-adrenoceptors mediate uterine relaxation in the pithed rat. They further show that the activity of compounds at these tissues can be used to assess their selectivity for beta 1- or beta 2-adrenoceptors in vivo.
Piercy
V
V
Beecham Pharmaceuticals Research Division, Biosciences Research Centre, Epsom, Surrey, UK.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta