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The pharmacological properties of SK&F 94120 on the cardiovascular system have been studied in laboratory animal species. The compound was shown to have positive inotropic activity on hearts from guinea-pig, cat, dog and marmoset in-vitro and in cat and dog in-vivo. These responses in-vivo occurred in association with minimal changes in heart rate. Positive(More)
These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a Ki for D2 receptors of 2.9 x 10(-8) M with no affinity for D1 at 10(-4) M in the rat. Ropinirole was weakly active at alpha 2-adrenoceptors and 5-HT2 receptors but inactive at 5-HT1, benzodiazepine and gamma-aminobutyric acid(More)
The cardiotoxicity and haemodynamic changes induced by IV administration of high doses of SK&F 94120, a novel positive inotrope/vasodilator, were studied in the dog. Inotropism was observed at a dose of 0.375 mg/kg. Mean blood pressure was reduced in a dose-related manner, reaching a nadir of 43.7 mm Hg at 24 mg/ kg. Heart rate was increased at doses of 1.5(More)
The properties of a new antihypertensive agent, SK&F 92657, D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied. The compound, given intravenously, subcutaneously, or orally, caused a sustained fall in systemic blood pressure of conscious genetically hypertensive rats, normotensive cats, and renal hypertensive dogs.(More)
Selective inhibitors of the cyclic nucleotide phosphodiesterase (PDE) isoenzymes have been studied to assess the potential for such agents in the treatment of asthma. A novel selective PDE V inhibitor, SK&F 96231, reversed the bronchoconstriction induced in anaesthetised guinea pigs by histamine, a thromboxane-mimetic or by ovalbumin challenge. There was no(More)
1. SK&F 94836 (racemate) was studied in vivo for its cardiovascular properties in cats and dogs. 2. In anaesthetized cats and dogs SK&F 94836 administered intravenously caused increases in left ventricular contractility and decreases in peripheral vascular resistance at similar doses, thus demonstrating the compound to be a mixed acting positive(More)
The beta-adrenoceptor-blocking properties of SK&F 92657, D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, were studied in both in vivo and in vitro. The pA2 against isoprenaline tachycardia (beta 1 effect) in isolated guinea pig right atria was 7.16 (6.14-7.87). In contrast, histamine-induced tachycardia was unaffected by SK&F 92657.(More)
Studies were conducted to determine possible development, and underlying mechanisms, of tolerance to the hypotensive effects of ropinirole (4-[2-(dipropylamino)ethyl]-1-3-dihydro-2H-indol-2-one HCl), a selective dopamine receptor agonist, following twice daily oral administration to cynomolgus monkeys and spontaneously hypertensive rats (SHR). Tolerance to(More)
1. SK&F 95654 inhibited the guanosine 3':5'-cyclic monophosphate (cyclic GMP)-inhibited phosphodiesterase (cGI-PDE) with an IC50 value of 0.7 microM. The IC50 values were greater than 100 microM for the other four phosphodiesterase isoenzymes tested. The R-enantiomer of SK&F 95654 (IC50 = 0.35 microM) was a more potent inhibitor of cGI-PDE than was the(More)
The haemodynamic and autonomic nervous system effects of the DA2 agonist, SK & F 101468, have been studied in anaesthetised cats. SK & F 101468 inhibited the tachycardia response to cardiac accelerans nerve stimulation. The inhibition, reversed by L-sulpiride a selective DA2 receptor antagonist, was dose-dependent over the dose range 10-50 micrograms.kg-1(More)