EFFECT OF AMEZINIUM METILSULFATE ON THE FINGER SKIN - VASOCONSTRICTORRESPONSE TO COLD STIMULATION AND VENOCONSTRICTOR RESPONSE TO NORADRENALINE

Orthostatic hypotension can be caused by an inadequate vasoconstrictor response. The effects of amezinium on vasoconstrictor response to sym pathetic stimulation and to exogenous noradrenaline were investigated and compared with those of midodrine. In 8 healthy men, the following experiments were performed after a single oral dose of 10 mg of amezin ium, 2 mg of midodrine or a placebo. First, finger-tip blood flow (FTB F) was recorded using a laser Doppler flowmeter before and during the contralateral hand cooling and a reduction ratio of FTBF was calculate d as an index of the vasoconstrictor response. Second, dose-response c urves to increasing doses (1-512 ng/min) of noradrenaline infused loca lly to the dorsal hand vein were determined using a linear variable di fferential transformer. The reduction ratio of FTBF was significantly increased (p<0.05) by amezimium [placebo, 75.9 +/- 9.8 (mean +/- SD)%; amezinium, 85.1 +/- 7.9%; midodrine, 78.1 +/- 9.3%]. The infusion rat e of noradrenaline producing a half-maximum venoconstriction was signi ficantly decreased (p<0.05) by amezinium (placebo, 40.6 +/- 33.9 ng/mi n; amezinium, 21.0 +/- 21.3 ng/min; midodrine, 33.2 +/- 31.5 ng/min). These findings indicate that amezinium increases the vasoconstrictor r esponse to sympathetic stimulation and to noradrenaline in normal subj ects, and this mechanism might contribute to the improvement by amezin ium of the symptoms of orthostatic hypotension.