HYPOTENSIVE EFFECT IN DOGS AND RATS OF INTRAVENOUS INJECTIONS OF THE 1-ADRENORECEPTOR ANTAGONIST BENOXATHIAN

The hypotensive effect of the alpha1-adrenoreceptor antagonist benoxathian has been evaluated in rats and dogs, in comparison to that evoked by WB 4101 and prazosin, In anaesthetized dogs, i.v. injection of benoxathian (25-100 g/kg), WB 4101 (5-25 g/kg) and prazosin (50g/kg) produced an immediate fall in diastolic blood pressure, which reached a maximum at about 30 sec after drug administration, whereas the hypotensive effect of prazosin persisted up to 3 hr following injection, the effect of both benoxathian and WB 4101 completely disappeared after 30-60 min. The hypotenslve effect of benoxathlan was dose-dependent. Pressor responses to i.v. noradrenaline (5g/kg), adrenaline (5g/kg) and phenylephrine (20 g/kg) were markedly inhibited (60-75%) by benoxathlan (100g/kg) whilst the pressor response to angiotensin II (0,05 g/kg) was not reduced, but indeed slightly increased. The hypotensive effect of benoxathian (100 g/kg) was abolished following pre-treatment with prazosin (50 g/kg) or hexamethonium (1000 g/kg). In anaesthetized rats similar results were obtained although recovery in blood pressure from the initial drop after i.v, injection of the drugs was slower than in dogs. Benoxathian was slightly more toxic than WB 4101 in rats. In conclusion, present findings show that benoxathlan causes a profound hypotensive effect in dogs and in rats through postsynaptic -adrenoreceptor blockade; however 1ts effect, as well as that of WB 4101, is shorter lasting than that of prazosln.