Biomedical subjects

L B Cobbin

Publications and source records attributed to L B Cobbin.

At least 19 recordsLinked to original sources

PubMed1987

Interaction of himbacine with carbachol at muscarinic receptors of heart and smooth muscle.

The interaction of himbacine with carbachol was studied and compared with that of homatropine in guinea-pig atria and rat stomach fundus. Himbacine was a competitive antagonist of carbachol in both preparations. In atria, himbacine had similar affinity for the muscarinic receptors associated with force (pA2 = 8.33) and rate of contraction (pA2 = 8.42). In stomach, himbacine had a pA2 value of 7.29 which corresponds to a 10-fold less affinity than for atria. In contrast, homatropine had similar affinities for muscarinic receptors in stomach (pA2 = 7.13) and for those in atria mediating force (pA2 = 7.21) and rate (pA2 = 7.07) responses. These results indicate that himbacine distinguishes between cardiac and smooth muscle muscarinic receptors whereas it is unable to distinguish between possible subtypes of cardiac receptors associated with force and rate responses.

Alkaloids↗

PubMed1986

The cardio-selectivity of himbacine: a muscarine receptor antagonist.

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.

Alkaloids↗

PubMed1976

Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and atrioventricular conduction.

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.

Animals↗

PubMed1974

Studies on the coronary dilator actions of some adenosine analogues.

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-beta-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-beta-D-arabinofurano-syladenine, tubercidin, N(6)-methyladenosine and 2-trifluoromethyl-N(6)-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.

Adenosine↗

PubMed1973