| Autor: |
Palm, D., Fengler, H. -J., Güllner, H. -G., Planz, G., Quiring, K., May, B., Helmstaedt, D., Lemmer, B., Moon, H. K., Holler, Ch. |
| Zdroj: |
European Journal of Clinical Pharmacology; March 1971, Vol. 3 Issue: 2 p82-92, 11p |
| Abstrakt: |
Investigations with an irreversible monoamine oxidase (MAO) inhibitor were performed in man in order to correlate biochemical, pharmacological, and clinical changes during and after MAO inhibition. — Six healthy volunteers were treated with the hydrazine MAO inhibitor benmoxine (1-a-methylbenzyl-2-benzoyl hydrazine) in a dosage of either 75 mg/day for 4 weeks, or with 75 mg/day for 2 weeks, and 100 mg and 125 mg per day during the 3rd and 4th week respectively. — 1. Inhibition of plasma MAO occurred rapidly and was almost complete after one week of treatment with 75 mg/day benmoxine. After discontinuation of the treatment, there was rapid normalization of enzyme activity (within one week) and a subsequent rebound. — 2. Inhibition of blood platelet MAO was also rapid and almost total, but the return to normal did not occur earlier than 3 weeks after cessation of the drug. — 3. The serotonin content of blood platelets increased cumulatively and dose-dependently during the treatment period. Normal serotonin levels were found 2–3 weeks after treatment was discontinued. — 4. Urinary tryptamine excretion was not increased when the lower benmoxine dose was given. An immediate threefold rise was observed with the higher dosage. This effect disappeared after about one week. — 5. Due to progressive MAO inhibition, the blood pressure rising effect of intravenously infused tyramine also increased cumulatively. This effect was dose-dependent: three- and fivefold potentiation were found after 4 weeks of treatment with the two different dosage schedules. — The mydriatic response to tyramine instilled into the conjunctival sac was also enhanced after 4 weeks of treatment. 6. Cardiovascular dysregulation could be detected (Schellong test, after exercise) only when the higher doses of inhibitor were given, i.e., after 4 weeks, when the pressure response to tyramine was increased to about 5 fold. — It is concluded that only the combined application of several methods (biochemical, pharmacological and clinical investigation procedures) permit definite conclusions to be drawn about the time course and extent of MAO inhibition in man. |
| Databáze: |
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