Effect of Amezinium Metilsulfate on the Finger Skin Vasoconstrictor Response to Cold Stimulation and Venoconstrictor Response to Noradrenaline

Abstract

hen a person assumes an upright posture, an increase of sympathetic outflow and an inhibition of parasympathetic activity occur reflexly, 1,2 which increases the heart rate and vascular resistance in order to maintain systemic blood pressure. Orthostatic hypotension may be caused by failure of these responses, 3,4 and for the treatment it is important to select a drug considering its pharmacological properties and the pathophysiology of the disease. At present, vasoconsticting agents are often used for the treatment of orthostatic hypotension. To understand the mechanism of these drugs, their effects not only on systemic blood pressure but also on the vasoconstrictor response to sympathetic stimulation should be examined. However, to our knowledge, such information is limited.Amezinium metilsulfate (amezinium) is one of the most popular drugs in Japan for the treatment of orthostatic hypotension. Amezinium has a unique mechanism of vasoconstriction; that is, it inhibits monoamine oxidase (MAO) activity and uptake of noradrenaline, 5,6 which prompted us to examine whether it influences the vasoconstrictor response to sympathetic stimulation and to -adrenoceptor stimulation by noradrenaline in humans.To examine the effects of the drug, the following 2 methods were thought to be suitable and were used in the present study, because they are sensitive and noninvasive and are used for the evaluation of autonomic disturbances or orthostatic hypotension. First, the finger-tip vasoconstrictor response to cold stimulation on the contralateral hand was examined using a laser Doppler flowmeter, which is an appropriate means for the study of the vasomotor response mediated by -adrenoceptor stimulation. 7,8 Second, the venoconstrictor response to locally infused noradrenaline was examined using a linear variable differential transformer (LVDT), which provides a sensitive and easy reproducible means of assessing the effect of a drug on peripheral veins. 9 As the decrease in venous blood return to the heart is involved in the pathogenesis of orthostatic hypotension, 3 it is interesting to also examine the effect of these drugs on veins.In the present study, we examined, using these methods, the effects of amezinium on the vasoconstrictor responses, and compared them in healthy subjects with those of midodrine hydrochloride (midodrine), an 1-adrenoceptor agonist, 10 which is also a popular drug for orthostatic hypotention. Methods SubjectsEight healthy Japanese males (21-26 years, 64-78 kg) were selected. They were normotensive and nonsmokers, without concomitant medication for at least 2 weeks before the study. The study was approved by the Ethical Committee of Jichi Medical School and all subjects gave their informed consent.Jpn Circ J 1998; 62: 824 -828 (Received April 10, 1998; revised manuscript received July 9, 1998; accepted July 14, 1998 Orthostatic hypotension can be caused by an inadequate vasoconstrictor response. The effects of amezinium on vasoconstrictor response to sympathetic stimulation and to exogenous noradre...