Inhibition of the Central Vasomotor Tone by Imipramine

Abstract

Imipramine, a potent antidepressant, has been reported to cause hypotension in cats when administered intravenously.The fall in blood pressure due to high doses of imi pramine has been attributed to adrenergic blocking action of the drug (1). Lower doses of imipramine (320 ag/kg i.v.) also cause hypotension although at this dose level it does not produce adrenergic blockade. The cause of hypotension due to low doses of imipra mine has still not been explored and the reported observations do not provide any ex planation for this response. The ganglion blocking and the adrenergic neurone blocking action of imipramine has been ruled out by the observations of Osborne and Sigg (1).Furthermore, they have ruled out acetylcholine like action of imipramine. The direct vasodilator effect of this drug has been excluded (2). These reports exclude the possibility of action of small dose of imipramine on the efferent limb of the reflex arc regulating blood pressure. It was, therefore, thought desirable to study the effect of imipramine on the medullary and spinal vasomotor loci. MATERIAL AND METHODSThe study was carried out on 21 adult cats of either sex, anaesthetised with pento barbitone sodium (35 mg/kg i.p.). The animals were routinely vagotomised and main tained on artificial positive pressure respiration. The blood pressure was recorded from right common carotid artery through a mercury manometer on smoked kymograph paper. A femoral vein was cannulated for intravenous injections. A cannula was passed in a lateral cerebral ventricle according to the technique of Feldberg and Sherwood (3). The total volume of fluid injected at a time did not exceed 0.25 ml. The excitability of the medullary vasomotor center was assessed by : A) Direct electrical stimulation of the vasomotor center by an stereotaxically orient ed bipolar stainless steel electrode according to the parameters described by Wang and Ranson (4). B) Reflex stimulation of the vasomotor center by :

Predominant Sensitivity to Tyramine in the Isolated Intermediate Auricular Artery of the Dog

“…Since tyramineinduced vasoconstriction was significantly suppressed when arterial preparations were taken from dogs pretreated with reserpine then tyramine might not have marked direct aadrenoreceptor stimulating properties as it does in the isolated basilar artery of the rabbit (Lee et al, 1981). Moreover, since imipramine has aadrenoreceptor blocking effects (Iversen, 1965;Jaju, Sinha & Srimal, 1967;Mandell, Spooner, Winters, Cruikshank & Sabbot, 1969;Shaikh, Gulati & Parikh, 1973;Puche, Morillas, Bolanos & Salvador, 1977), the potentiating action of imipramine on noradrenaline-induced responses may be masked in the present study.…”

An Analysis of the Central Vasomotor Effects of Monoamine Oxidase Inhibitor, Modaline Sulphate

“…Moreover, other MAO inhibitors like iproniazid and pheniprazine were found to inhibit hypothalmic and brain stem vasomotor loci (6). Furthermore, this delayed stimulant effect of modaline sulphate on the central vasomotor loci was not due to its imipramine like activity on the CNS (2) since imipramine was found to inhibit medullary vasomotor loci (5). Similarly, an activation of cholinergic mechanism in CNS for this delayed rise in the blood pressure was unlikely as it was not blocked by prior central atro pinization.…”

“…Both imipramine and MAO inhibitors viz. pheniprazine and iproniazid were found to inhibit the excitability of the hypothalmic and brain stem vasomotor loci (5,6). On the other hand, modaline potentiated the facili tation of monosynaptic spinal reflexes induced by stimulation of brain stem reticular for mation (7).…”

Antiacetylcholine Action of Imipramine

“…Imipramine produced a depressor effect on the blood pressure in all the animal species studied. At a lower dose level the depressor action has been attributed to a central vaso depressor effect (5). On the other hand, Sigg et al (3) have attributed the hypotensive action of imipramine at a relatively higher dose level to a direct depressant action on the myocardium.…”