Robertson Towart

Nimodipine inhibits carbocyclic thromboxane-induced contractions of cerebral arteries

Carbocyclic thromboxane A2 (CTA2) constricted rabbit basilar and saphenous arteries. The contractions of the basilar artery, but not those of the saphenous artery, were potently inhibited by the calcium antagonist nimodipine. Selective inhibition of thromboxane-induced vasoconstriction of cerebral vessels may contribute to the beneficial actions of calcium antagonists in models of cerebral ischaemia or vasospasm.

Effects of unsymmetrical ester substituted 1,4-dihydropyridine derivatives and their optical isomers on contraction of smooth muscle

SummaryThe optical isomers of two nifedipine-like 1,4-dihydropyridine derivates have been synthesised and tested in vitro. The (−)-isomer (S-configuration of both compounds) was more potent than the racemate, which in turn was more potent than the (+)-isomer (R-configuration). The S-configuration isomers are approximately ten times more potent than nifedipine, and may represent the optimal structure and configuration for binding to and inhibiting calcium channels.

Correlation between the inhibitory activities of calcium entry blockers on vascular smooth muscle constriction in vitro after K+-depolarisation and in vivo afterα2-adrenoceptor stimulation

SummaryCalcium entry blockers are known to depress the maximal increase in diastolic pressure induced in pithed rats by selective α2-adrenoceptor stimulation. In order to substantiate the relevance of calcium fluxes in this interaction, a correlation between the potency of calcium entry blockers in pithed rats and their calcium antagonistic potency in vitro was investigated. Accordingly, the inhibition of calcium entry blockers with respect to α2-adrenoceptor-mediated vasoconstriction was quantified in terms of −log ID50 values. As a measure of calcium antagonistic potency, the inhibitory activity of a number of calcium entry blockers on K+-induced contractions of rabbit thoracic aorta strips was determined and the negative logarithms of the 50% inhibitory concentrations, −log IC50, were calculated. A highly significant linear relationship was found between the in vitro, −log IC50, and the in vivo parameter, −log ID50, of the calcium entry blockers. This result suggests a similar type of interaction for the calcium entry blockers in vivo and in vitro, i.e. inhibition of a transmembrane influx of extracellular calcium.

Relaxation of carbocyclic thromboxane A2-induced contractions of isolated coronary arteries by nifedipine.

Summary± Carbocyclic thromboxame A2 (2.9×10−7 mol/l) contracted isolated rings of cat coronary artery. These contractions could be partly inhibited by low concentrations of nifedipine (50% inhibitory concentration —IC50=6.8×10−8 mol/l) and completely relaxed by papaverine. Relaxation of thromboxane-induced coronary spasm may contribute to the effectiveness of calcium antagonists in variant angina, which may be caused or exacerbated by thromboxane A2 release from platelets.

An integrated mini-computer system for the automatic control of pharmacological experiments and calculation of results

A mini-computer system for the automation of pharmacological experiments and for the calculation, printing and storing of results is described. A link between the 1) control unit which powers the pumps, valves, etc., and 2) the computer which processes the digital data allows the synchronization of data collection with the time course of the experiment. Thus results may be immediately expressed in absolute (i.e. stimulus-induced change in tension, etc.) or relative (i.e. % change in response due to drug administration) terms.