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A method for the differentiation of presynaptic inhibitors of adrenergic neurotransmitter release

Natoff, I.L.; Dodge, B.B.

Journal of Pharmacological Methods 3(2): 159-165

1980


ISSN/ISBN: 0160-5402
PMID: 6104749
DOI: 10.1016/0160-5402(80)90025-x
Accession: 042075258

Injection of clonidine hydrochloride, 30 microgram/kg iv, or bretylium tosylate, 5 mg/kg iv, in pithed male spontaneously hypertensive rats inhibits the pressor responses to stimulation of the total sympathetic outflow, and enhances those to injected noradrenaline. The intravenous injection of d-amphetamine sulphate, 200 microgram/kg, reverses bretylium inhibition of the responses to sympathetic stimulation but not that of clonidine. Yohimbine, 10 microgram/kg/min iv on the other hand, reverses clonidine inhibition of the responses to sympathetic stimulation, but not that of bretylium. This pharmacological analysis provides a method for the differentiation of the mechanism of effect of two types of antihypertensive drug which act presynaptically to impair the release of the neurotransmitter from sympathetic nerves, viz., sympathetic neurone blocking agents (such as bretylium tosylate) and presynaptic alpha-adrenoceptor stimulants (such as clonidine hydrochloride).

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