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  • Title: Pre- and postsynaptic alpha-adrenergic effects of the antihypertensive drug budralazine.
    Author: Shibamura S, Chiba T, Suzuki I, Akashi A.
    Journal: Arzneimittelforschung; 1981; 31(7):1076-9. PubMed ID: 6268123.
    Abstract:
    Cardiac presynaptic and vascular postsynaptic alpha-adrenergic effects of 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) were studied in comparison with those of hydralazine. Budralazine was about 3 times less potent than hydralazine in producing tachycardia in spontaneously hypertensive and normotensive rats when compared at equihypotensive doses. In normotensive pithed rats, budralazine at 3 mg/kg i.v. affected neither the tachycardiac response to cardioaccelerator nerve stimulation nor the inhibition of clonidine of the stimulation-induced tachycardia. As the dose was increased to 6 and 12 mg/kg i.v., however, budralazine not only inhibited transiently the sympathetic tachycardia but also enhanced the clonidine bradycardia, although this drug was almost without effect on resting heart rate. These effects of budralazine on the heart rate response in the stimulated rats were partially but significantly antagonized by pretreatment with phentolamine. Hydralazine (3 mg/kg i.v.) differed from budralazine in that its transient inhibition of the stimulation-induced tachycardia was not modified by phentolamine and it produced an acceleration of the recovery of clonidine bradycardia as well as an increase in resting heart rate. Budralazine (3--12 mg/kg i.v.), like hydralazine (0.3 and 3 mg/kg i.v.), antagonized pressor responses to noradrenaline and phenylephrine but did not affect the tachycardia produced by both agonists in normotensive pithed rats. Based on these results, a possible mechanism of hypotensive and weak tachycardiac actions of budralazine is discussed in relation to that of hydralazine.
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