Effects of LM 5008, a selective inhibitor of 5‐hydroxytryptamine uptake, on blood pressure and responses to sympathomimetic amines

Abstract

1 LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) (10,20 and 50 mgkg-) had no significant effect on pressor responses to noradrenaline or tyramine in rats anaesthetized with urethane. Desmethylimipramine (1 mg kg-1) blocked the response to tyramine but chlorimipramine (5 mg kg-1) had no significant effect on responses to noradrenaline or tyramine. 2 In the rabbit, anaesthetized with chloralose, LM 5008 (5 mg kg-') had no effect on pressor responses to noradrenaline, tyramine or angiotensin II, while desmethylimipramine (0.25 mg kg-1) inhibited responses to tyramine and potentiated those to noradrenaline.3 LM 5008 (10mg kg-') had no effect on resting blood pressure of conscious normotensive or DOCA-saline hypertensive rats. 4 Tranylcypromine (5 mg kg-) produced a fall in blood pressure in conscious normotensive and in DOCA hypertensive rats.5 Treatment with a combination of LM5008 (10mgkg-t) and tranylcypromine (5mgkg-1) resulted in the appearance of a behavioural hyperactivity syndrome, but blood pressure was not different from that of animals treated with tranylcypromine alone. 6 These results further demonstrate the selectivity of LM 5008 for 5-hydroxytryptamine as opposed to catecholamine uptake.

5‐Hydroxytryptamine‐induced tachycardia in the pig: possible involvement of a new type of 5‐hydroxytryptamine receptor

“…increase in cardiac output, since it was eliminated after additional administration of propranolol. Lastly, indalpine and fluvoxamine, which are known to interfere with the uptake of 5-HT by nerve terminals and blood platelets (Claasen et al, 1977;Le Fur & Uzan, 1977;Ashkenazi et al, 1983), were employed in an attempt to antagonize the tachy- 50L a Before cardiac responses to 5-HT. However, after administration of these drugs the positive chronotropic responses to bolus injections of 5-HT were not reduced, but, on the contrary, these responses were facilitated both in magnitude and in duration (see Figure 2 for indalpine and Table 3 for The effects of 5-hydroxytryptamine (5-HT; 3, 10 and 30pgkg-1) on heart rate in an anaesthetized pig before (a) and after (b) administration of indalpine (1 mgkg-1).…”

“…If an unidentified neurotransmitter is indeed displaced and released by 5-HT, this would involve an uptake process that is distinct from the one selectively inhibited (in the brain and blood platelets) by indalpine (Le Fur & Uzan, 1977;Ashkenazi et al, 1983) and fluvoxamine (Claasen et al, 1977) since these drugs increased (not reduced) the magnitude and duration of 5-HTinduced tachycardia. Though such a possibility cannot be entirely dismissed, it is perhaps more likely that the tachycardia elicited by 5-HT is mediated by a receptor type which is different from those characterized so far, i.e.…”

Multimodal serotonergic antidepressants

“…Сразу после начала использования в клинической практике зимелидина и индалпина в 1982-1983 гг. тразодон был объединен с ними в группу СИОЗС [19]. Установление в конце 80-х годов способности нефазодона ингибировать обратный захват серотонина также позволило причислить его к группе СИОЗС [20].…”