Verapamil (Isoptin) caused a dose-dependent peripheral vasodilation, increase in myocardial contractility, and tachycardia in the anaesthetized dog. Propranolol pretreatment blocked the cardiac stimulation following verapamil but the vasodilation was unaltered. Inflation of a thoracic aortic balloon prevented the fall in intravascular pressure and reduced the tachycardia and positive inotropic responses. These experiments suggest that clinical doses of verapamil cause peripheral vasodilation which leads to a sympathetic reflex induced increase in heart rate and myocardial contractility. Verapamil also had a direct myocardial depressant action which became evident at doses above the range used clinically. The drug increased the PR interval in conscious dogs for up to 60 minutes. This effect was partly mediated through cholinergic stimulation and partly through a direct depression on atrioventricular conduction.

The antimuscarinic actions of himbacine were compared with those of atropine and/or homatropine on atria, ileum and trachea from guinea-pigs and rat uterus preparations. The antagonism of acetylcholine or carbachol by all the antagonists was competitive on the preparations studied. The pA2 values of himbacine in all smooth muscle preparations were similar (around 7.2) whereas in atria it exhibited about 10-fold higher affinity (pA2 = 8.2). In contrast, both atropine and homatropine had similar affinities for muscarine receptors (pA2 values around 9.1 and 7.2 respectively) in both atria and smooth muscle. It may be concluded from these results that cardiac and smooth muscle muscarine receptors are not homogeneous and that himbacine is a relatively potent and selective antagonist for cardiac receptors. The cardio-selectivity of himbacine supports the concept of heterogeneity of muscarine receptors.

1 The cardiovascular actions of 23 adenosine analogues have been examined in anaesthetized open thorax dogs; the analogues were substituted in the 2-position of the purine ring, or in the exocyclic amino group, or were modified in the imidazole or sugar rings. 2 The effects of these compounds on coronary blood flow, peripheral blood pressure, and heart rate were compared with those of adenosine.3 9-0-D-Arabinofuranosyladenine had no cardiovascular action; the other analogues on intra-atrial administration caused an immediate increase in coronary blood flow, the magnitude and duration of which varied with the structures of the analogues. 4 2-Fluoro-, 2-bromo-, 2-isobutylthio-, 2-ethylamino-, and 5'-deoxy-5'-chloro-adenosines had coronary dilator potencies equal to or greater than that of adenosine. No relationship was found between the dilator potency of the adenosine analogues and their duration of coronary dilator action.5 The coronary dilator action of adenosine was potentiated by inosine, 9-0-D-arabinofuranosyladenine, tubercidin, N6 -methyladenosine and 2-trifluoromethyl-N6-methyladenosine. 6 There was no correlation between the substrate specificities of the shorter-acting analogues for adenosine deaminase or adenosine kinase and their duration of coronary dilator action. 7 It is proposed that in the anaesthetized dog, uptake into tissues is a more important mode of removal of adenosine and adenosine analogues from the vascular system than inactivation by adenosine deaminase, that the duration of coronary dilator action of the analogues is related primarily to their specificity for the carrier which mediates adenosine uptake, and that the adenosine carrier is not associated with kinase action.

No abstract

No abstract

4. In all cases 2-substitution prolonged the duration of the coronary dilator activity of adenosine. 5. N6-Methylation of adenosine and 2-chloroadenosine reduced their coronary dilator activities, but had no effect on the duration of the response. 6. Comparison of the coronary dilator potencies and hypotensive activities of 2-ethylaminoadenosine and 2-methoxyadenosine indicates that these analogues have some specificity for the coronary bed.

No abstract

A substance has been demonstrated in acetone extracts of freeze‐dried spleen which had cardiotonic properties on isolated papillary muscles from the cat and perfused hearts of the cat and guinea‐pig. This activity of the extract could not be explained by the presence of choline, acetylcholine, histamine, 5‐hydroxytryptamine, adrenaline or noradrenaline.