The alpha(1)-adrenoceptor-antagonistic and steroid 5 alpha-reductase-inhibitory actions of Z-350 ([S)-4-{3-{4-{1 -(4-methylphenyl)-3-[4(2-methoxyphenyl)piperazine-1 -yl]propoxy}benzoyl}indole-1-yl}butyric acid hydroch...
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The alpha(1)-adrenoceptor-antagonistic and steroid 5 alpha-reductase-inhibitory actions of Z-350 ([S)-4-{3-{4-{1 -(4-methylphenyl)-3-[4(2-methoxyphenyl)piperazine-1 -yl]propoxy}benzoyl}indole-1-yl}butyric acid hydrochloride] were investigated in rabbits and rats in vivo. Z-350 (1-30 mg/kg), administered intraduodenally, dose-dependently inhibited phenylephrine-induced increases in prostatic urethral pressure with an ED,, value of 3.8 mg/kg in anesthetized male rabbits, whereas the effects on mean blood pressure and orthostatic hypotensive response were weaker when compared with other alpha(1)-adrenoceptor antagonists, tamsulosin and prazosin. Z-350 (1-10 mg/kg p.o.) dose-dependantly inhibited the prostatic steroid 5 alpha-reductase activity in rats with an ED50 value of 2.8 mg/kg. The daily oral administration of Z-350, at greater than or equal to 10 mg/kg for 7 days, significantly reduced the prostatic growth induced by testosterone in castrated rats, with no effect on dihydrotestoterone-induced prostatic growth. These results indicate that Z-350 exhibited alpha(1)-adrenoceptor-antagonistic and 5 alpha-reductase inhibitory actions at almost equal doses in vivo, and was expected to improve the bladder outlet obstruction associated with benign prostatic hyperplasia with smaller cardiovascular adverse effect.
There is no single drug that proved effective in the treatment of orthostatic hypotension. Oral sympathomimetics like ephedrine, wyamine, aramine, and similar drugs are generally prescribed but, in our experience, the...
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There is no single drug that proved effective in the treatment of orthostatic hypotension. Oral sympathomimetics like ephedrine, wyamine, aramine, and similar drugs are generally prescribed but, in our experience, their effectiveness is unpredictable; however they should be given a trial. Mineralocorticoids have already been referred to, 9 α fluorohydrocortisone (Florinef) is the one we use. Besides producing salt and water retention and expanding the blood volume, an effect which helps venous filling of the heart, it may increase the responsiveness of arterioles to the neurotransmitter. Recently there are claims that tyramine rich foods combined with monoamine oxidase inhibitors are effective in the treatment of resistant cases of IOH, but results were not encouraging when this regimen was tried in two of our patients. All kinds of drug therapy carry the danger of precipitating hypertension. Frequent observation of arterial pressure at weekly intervals is recommended. When Florinef is prescribed one should start with a small dose (0.1 mg. per day) which can be increased gradually according to therapeutic response. In conclusion the treatment of orthostatic hypotension still presents a challenging problem. The aim should be to keep the patient active and ambulatory as long as possible.
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