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

LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) (10, 20 and 50 mg kg-1) 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. In the rabbit, anaesthetized with chloralose, LM 5008 (5 mg kg-1) 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. LM 5008 (10 mg kg-1) had no effect on resting blood pressure of conscious normotensive or DOCA-saline hypertensive rats. Tranylcypromine (5 mg kg-1) produced a fall in blood pressure in conscious normotensive and in DOCA hypertensive rats. Treatment with a combination of LM 5008 (10 mg kg-1) and tranylcypromine (5 mg kg-1) resulted in the appearance of a behavioural hyperactivity syndrome, but blood pressure was not different from that of animals treated with tranylcypromine alone. These results further demonstrate the selectivity of LM 5008 for 5-hydroxytryptamine as opposed to catecholamine uptake.