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  • Title: Pharmacological properties of (N-dicyclopropylmethyl) amino-2-oxazoline (S 3341), an alpha-2 adrenoceptor agonist.
    Author: Laubie M, Poignant JC, Scuvée-Moreau J, Dabire H, Dresse A, Schmitt H.
    Journal: J Pharmacol; 1985; 16(3):259-78. PubMed ID: 2866274.
    Abstract:
    Pharmacological actions of (N-dicyclopropylmethyl)-amino-2-oxazoline (S 3341), an agonist of alpha-2 adrenoceptors, were examined in acute animal studies. In the normotensive anaesthetized dog S 3341 (0.3 mg/kg, i.v.) produced an initial transient increase followed by a marked, prolonged fall in mean arterial pressure (MAP) of 20 mmHg. Central actions of S 3341 were demonstrated by administration of low doses into the vertebral artery of the anaesthetized dog. A rapid and marked fall in MAP resulted which was antagonised by piperoxan. Splanchnic discharges were strongly decreased following S 3341 i.v. administration, suggesting a centrally mediated diminution of sympathetic tone. Peripheral actions of S 3341 were observed in the pithed rat where a dose-dependent increase in MAP was noted which was somewhat antagonised by prazosin and largely by prazosin plus yohimbine. S 3341 reduced hypertension and tachycardia due to stimulation of the sympathetic outflow in the pithed rat, an effect also antagonised by piperoxan. These effects were more marked and prolonged than those of clonidine. S 3341 reduced the tachycardia resulting from stimulation of the cardioaccelerator nerve in the anaesthetized, spinalised and bilateraly vagotomised dog, this effect was reversed by piperoxan. S 3341 did no change the tachycardia induced by noradrenaline or tyramine. Plasma renin activity was significantly decreased after S 3341 treatment in dogs on low normal or high sodium diets. In rats S 3341 decreased the rate of discharge of noradrenergic cells located in the locus coeruleus which are believed to be involved in wake/sleep mechanisms. This depression was 63 times less than that of clonidine. At effective hypotensive doses S 3341 produced no sedation (i.e. loss of righting reflex) in 2 day old chicks. In addition the sedative action of clonidine was inhibited by S 3341 pretreatment. In the mouse tail flick model, the antinociceptive effects of S 3341 were 45 times less than those of clonidine. S 3341, an oxazoline derivative, appears to have haemodynamic effects similar to those of other agonists of central alpha-2 adrenoceptors but with fewer side-effects, and therefore could be of interest an as antihypertensive agent.
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