Effects of oxyfedrine on isolated portal vein and other smooth muscles

Abstract

Summary1. Oxyfedrine (0O01-1P0 ,g/ml), inhibited spontaneous myogenic activity in rat isolated portal vein and carbachol-induced contractions of rat isolated uterus, and relaxed the rabbit duodenum and the guinea-pig tracheal chain preparation. These actions were prevented by the f8-adrenoceptor blocking drug alprenolol. Oxyfedrine was a relatively weak ,3-adrenoceptor stimulant (10-100 times less active than isoprenaline) but its actions were more prolonged. 2. In the same concentrations, oxyfedrine reduced or prevented the inhibition of myogenic activity of the rat portal vein induced by isoprenaline and by repeated doses of oxyfedrine itself, acting as a partial agonist at f3-adrenoceptor sites. 3. Oxyfedrine, 1-12 ,ug/ml increased myogenic activity in the rat portal vein. This effect was not due to direct or indirect stimulation of a-adrenoceptors (because it was unaffected by phentolamine) or to potentiation of acetylcholine or 5-hydroxytryptamine. 4. Oxyfedrine (>20 ,g/ml) inhibited spontaneous myogenic activity in the portal vein and relaxed the saphenous vein contracted with noradrenaline. This spasmolytic effect of the drug was not due to 8-adrenoceptor stimulation or to inhibition of phosphodiesterase since it was unaffected by alprenolol and by concentrations of imidazole which antagonized the effects of the active phosphodiesterase inhibitor, papaverine. In the portal vein this effect of oxyfedrine was similar to that of the calcium inhibitor iproveratril; some of the effects of oxyfedrine on venous smooth muscle may be mediated through effects on calcium transport.

The HAEMODYNAMIC EFFECTS OF PROLONGED ORAL ADMINISTRATION OF OXYFEDRINE, a PARTIAL AGONIST AT Β‐ADRENOCEPTORS: COMPARISON WITH PROPRANOLOL

“…Thus, marked increases in left ventricular dP/dt max, heart rate and cardiac output occur with very little peripheral vasodilatation (Moore & Parratt, 1972 and Table 2). We should nevertheless hesitate to call oxyfedrine a 'specific' Il -stimulant (Osswald & Guimires, 1971) since, at least in isolated tissues, there is ample evidence that the drug causes a long-lasting stimulation of both f3and 32 -adrenoceptors in similar concentrations (Beckett & Foster, 1972;Mackenzie & Parratt, 1973). In view of the degree of (-adrenoceptor blockade achieved with both oxyfedrine and propranolol it was perhaps surprising that the acute stimulant effects of oxyfedrine were unaffected by long-term treatment with oxyfedrine (Table 2) or with propranolol.…”

“…It exerts sympathomimetic effects on atria, and on a variety of vascular and non-vascular smooth muscle preparations, in similar concentrations to those which antagonize the effects of 13-adrenoceptor stimulants such as isoprenaline (Beckett & Foster, 1972, 1973Mackenzie & Parratt, 1973;Sakai, Shiraki & Hashimoto, 1973). There is some evidence from double-blind trials that oxyfedrine is an effective anti-anginal drug (Greif & Liertzer, 1967;Stampfer, 1969;Marner, 1970; Raisp, 1970).…”

Cardioprotection by oxyfedrine in hereditary cardiomyopathic hamsters

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A defect of the myocardial plasma membrane, resulting in increased transmembrahe calcium conductivity with consecutive myocardial calcium accumulation and exhaustion of high energy phosphates is considered the determinant factor for cardiac degeneration in the dystrophic cardiomyopathy of Syrian hamsters from strain BIO 8262. Pharmacologically it is described as a partial ~-adrenoceptor agonist inducing simultaneous stimulation of ~-adrenoceptors and blockade of catecholamines at adequate concentrations and a quinidine-like effect on cardiac and smooth muscle at higher concentrations (14,2,38,28, 11). By chronical subcutaneous injection of 30 mg/kg oxyfedrine twice daily it was possible to avoid spontaneous myocardial calcium accumulation as well as to nearly prevent degeneration of the myocardium.

These findings suggest that oxyfedrine exerts cardioprotection by its calcium antagonistic properties.

The aminoketone derivative oxyfedrine (L-3-[~-hydroxy-a-methylphenethylamino]-3'-methoxy-propiophenone hydrochloride) is clinically used as a drug against coronary heart disease (42,39,36,15,44,13,27).

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