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1 The cardiovascular and sedative effects of FLA-136 have been compared with those of clonidine after intracerebroventricular (i.c.v.) administration in the rat. The effects of both drugs on pre-and postsynaptic a-adrenoceptors in the periphery have been investigated after intravenous (i.v.) administration in the pithed rat. 2 In the anaesthetized rat, i.c.v. FLA-136 and clonidine produced dose-related hypotension, FLA-136 having three to 30 times less activity than clonidine; both drugs caused concomitant bradycardia. In the conscious rat i.c.v. FLA-136 had less sedative potential than clonidine, in terms of overt sedation assessed visually. 7 FLA-136, unlike clonidine, did not stimulate peripheral pre-or postsynaptic a-adrenoceptors in the pithed rat. 8 FLA-136 is a novel centrally-acting hypotensive compound which, unlike clonidine, selectively stimulates central a-autoreceptors (yohimbine-sensitive) in the rat; these autoreceptors may be different from peripheral pre-and postsynaptic a-adrenoceptors. The results suggest that clonidine lowers blood pressure by stimulation of two types of central postsynaptic x-adrenoceptors in the rat; one type being sensitive to yohimbine and the other to prazosin.

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