A comparison of the cardiovascular actions of AQ 110 with those of isoprenaline and salbutamol

Abstract

Summary1. AQ 110 is a 3-adrenoceptor agonist which, like isoprenaline and salbutamol, acts directly on the receptors. 2 Compared with isoprenaline, AQ 110 has relatively stronger actions on bronchial and vascular smooth muscle (P2-adrenoceptors) than stimulant effects on heart muscle (ft1-adrenoceptors). The fl2-selectivity of AQ 110 is, however, much less than that of salbutamol, mainly due to the weak cardiac actions of the latter.3. At doses which were equipotent in decreasing the bronchoconstrictor effect produced by a standard dose of 5-hydroxytryptamine, AQ 110 had marginally less hypotensive action than salbutamol and considerably less than isoprenaline. 4. Although AQ 110, unlike salbutamol, possesses a catechol group it was found not to be a substrate for catechol-O-methyl transferase and this is considered to account for its significantly prolonged action, compared with isoprenaline, in vivo.

Salbutamol

“…The hypotensive effect could be blocked by propranolol, but was not altered in reserpine pre-treated cats (Fogelman and Grundy, 1970). The hypotensive threshold for isoprenaline was 10 to 50 ng and for salbutamol 125 ng to 1,000 ng.…”

“…In the perfused rabbit ear it was 10 and in the isolated rabbit ear artery preparation it was 11 times less active as a vasodilator than isoprenaline (Fogelman and Grundy, 1970). These effects could be inhibited by propranolol (Cullum et al, 1969;Fogelman and Grundy, 1970). Salbutamol had 137 times less activity than isoprenaline in contracting rabbit portal (anterior mesenteric) venous strips; this effect could be inhibited by phentolamine, thus indicating an a-adrenergic receptor response.…”

“…These effects could be inhibited by propranolol (Cullum et al, 1969;Fogelman and Grundy, 1970). However, after inducing contraction with noradrenaline, acetylcholine or 5.hydroxytryptarnine, salbutamol relaxed both the portal vein (48 times less active than isoprenaline) and thoracic aortic strips (11 times less active than isoprenaline); these effects were antagonised by propranolol, thus indicating a ,l3-adrenergic receptor response (Fogelman and Grundy, 1970). Salbutarnol, unlike isoprenaline, had no effect on thoracic aortic strips.…”

“…In another experiment involving only 3 observations, salbutamol had at least 500 times less activity than isoprenaline in increasing the rate and force of contraction of the isolated guinea-pig heart (Fogelman and Grundy, 1970). Salbutamol was 400 times less potent than isoprenaline in activating cardiac phosphorylase in the rat ; the effect of both drugs being blocked by propranolol (McNeill and Cammarata, 1970) .…”

Cardiovascular effects of morphine, pethidine, diamorphine and nalorphine on the cat and rabbit

“…The methods used were essentially those of Fogelman & Grundy (1970). In the guinea-pig heart, drugs were generally injected at not less than 10 min intervals.…”