title: Effect of amezinium metilsulfate on the finger skin vasoconstrictor response to cold stimulation and venoconstrictor response to noradrenaline.
abstract: Orthostatic hypotension can be caused by an inadequate vasoconstrictor response. The effects of amezinium on vasoconstrictor response to sympathetic 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 10mg of amezinium, 2mg of midodrine or a placebo. First, finger-tip blood flow (FTBF) was recorded using a laser Doppler flowmeter before and during the contralateral hand cooling and a reduction ratio of FTBF was calculated as an index of the vasoconstrictor response. Second, dose-response curves to increasing doses (1-512ng/min) of noradrenaline infused locally to the dorsal hand vein were determined using a linear variable differential 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 rate of noradrenaline producing a half-maximum venoconstriction was significantly decreased (p<0.05) by amezinium (placebo, 40.6 +/- 33.9 ng/min; amezinium, 21.0 +/- 21.3 ng/min; midodrine, 33.2 +/- 31.5 ng/min). These findings indicate that amezinium increases the vasoconstrictor response to sympathetic stimulation and to noradrenaline in normal subjects, and this mechanism might contribute to the improvement by amezinium of the symptoms of orthostatic hypotension.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Ohmori
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D005385:Fingers / Q000098:blood supply; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy; D007564:Japan; D008297:Male; D008879:Midodrine / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D013566:Sympathomimetics / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D008996:Monoamine Oxidase Inhibitors; D011724:Pyridazines; D013566:Sympathomimetics; D014662:Vasoconstrictor Agents; D008879:Midodrine; C027784:amezinium; D009638:Norepinephrine