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  • Title: Studies on the specificity of the inhibitory action of N,N-diisopropyl-N'-isoamyl-N'-diethylaminoethylurea (P-286) on adrenal catecholamine release in the anaesthetized rat.
    Author: Malta E, Angus JA.
    Journal: Clin Exp Pharmacol Physiol; 1988 Nov; 15(11):815-25. PubMed ID: 3229006.
    Abstract:
    1. The ability of P-286 (N,N-diisopropyl-N'-isoamyl-N'-diethylaminoethylurea) to reduce selectively the release of catecholamines from the adrenal medulla has been studied in urethane-anaesthetized rats. 2. Pressor responses to acetylcholine (Ach) and the nicotinic receptor-agonist 1,4-dimethylphenylpiperazine (DMPP) in rats treated with atropine, (+/-)-propranolol and guanethidine were used as the index of adrenal catecholamine release. 3. The injection of P-286 (1-10 mg/kg, i.v.) elicited a dose-dependent bradycardia which was associated with hypotension. P-286 reduced pressor responses to Ach and DMPP in a dose-dependent manner with an IC50 of 2.5 mg/kg and, following near complete blockade, pressor responses to DMPP returned to 50% of control after 90 min. 4. In non-atropinized rats, P-286 (30 mg/kg, i.v.) was without effect on the bradycardic responses elicited by stimulation of the right vagus nerve at frequencies of 5-40 Hz while pressor responses to DMPP in bilaterally adrenalectomized, non-guanethidine treated rats were reduced by approximately 50% after P-286 (10 mg/kg, i.v.). 5. The latter effect of P-286 on responses to DMPP in adrenalectomized rats cannot be attributed to ganglionic blockade since in rats with intact adrenals P-286 (10 mg/kg, i.v.) also reduced pressor responses to i.v. adrenaline and i.v. angiotensin II by approximately 50%. Thus the reduction in response to DMPP in adrenalectomized rats and to the non-nicotinic agonists may be a reflection of an action on the mechanism of contraction of vascular smooth muscle; that is, at a post-receptor event. 6. The results of the study show that P-286 selectively reduces adrenal catecholamine release at doses which do not affect autonomic ganglia. Its usefulness as a tool in cardiovascular research, however, may be limited by an action of vascular smooth muscle.
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