In vitro and in vivo α-blocking activity of thymoxamine and its two metabolites

Author:

Creuzet M H1,Prat G1,Malek A2,Fauran F1,Roquebert J2

Affiliation:

1. Sarget Research Department, Avenue J. F. Kennedy, 33701 Merignac, France

2. Laboratory of Pharmacology, University of Bordeaux II, Rue Leyteire 33000, Bordeaux, France

Abstract

Abstract The α-adrenoceptor potency of thymoxamine and its two metabolites deacetylthymoxamine and demethyldeacetylthymoxamine were determined on the contraction of rat vas deferens induced by noradrenaline, the blood pressure increase induced by noradrenaline given i.v. to dogs and the contraction of the nictitating membrane induced by electrical stimulation in cats. In vivo the three drugs were administered at 6·35 times 10−6 mol kg−1 intravenously. Deacetylthymoxamine presented nearly the same α-blocking activity as the parent drug. This was ascribed in vivo to the rapid deacetylation of thymoxamine. Demethyldeacetylthymoxamine was less active. In vitro its pA2 was 6·20 ± 0·09 compared with 6·75 ± 0·20 for thymoxamine and 6·57 ±0·13 for deacetylthymoxamine. In vivo, it was inactive in dog and less active than the other two drugs soon after its administration in the cat. The oral LD 50 values in the mouse for the three drugs were respectively 0·81, 0·71 and 1·14 mmol kg−1 for thymoxamine, deacetylthymoxamine and demethyldeacetylthymoxamine.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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