[On the pharmacodynamics of acemetacin (author's transl)].

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Jacobi H, Dell HD

[On the pharmacodynamics of acemetacin (author's transl)].

Arzneimittelforschung. 1980;30(8A):1348-62.

PubMed ID
6968219 [ View in PubMed
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Abstract

Pharmacodynamic studies were carried out on (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]acetic acid (acemetacin, TV 1322, Rantudil), a new strongly acting non-steroidal anti-inflammatory agent for elucidation of its mechanism of action. Despite its strong anti-inflammatory activity, acemetacin is only a weak inhibitor of prostaglandin release. Release of histamine from mast cells induced by N-methylhomoanisylamine-formaldehyde condensate (compound 48/80) was strongly inhibited by acemetacin in a dose dependent manner. It was also highly effective in in vitro tests, for example, in the protein turbidity test of Mizushima. In accordance to the weak inhibition of prostaglandin release very little damage was done to the mucous membrane of the gastrointestinal tract by this anti-inflammatory agent. From these data and from the strong anti-inflammatory activity a broad therapeutic margin can be derived. Analgetic properties were shown in the benzoquinone test after oral and in the Randall-Selitto test after i.m. application. Hyperthermia caused by Pyrifer and by yeast is inhibited by acemetacin in a dose dependent manner. Corresponding to the weak influence on prostaglandin release the reduction of diuresis by acemetacin was only small. No tocolytic effect could be detected on the gravid uterus in vitro. Function of the heart (isolated heart of guinea-pig) was unaffected, but we registered an increase in sytolic and diastolic blood pressures in the anesthetized dog. Correspondingly, left ventricular pressure also increased, these changes were accompanied by bradycardia. Coronary flow, peripheral flow and dp/dt did not change, only the pressure in the right atrium rose slightly. In cats, acemetacin caused a short-lasting decrease in the arterial blood pressure. Effects on CNS were not found. Smooth muscles (bronchial/intestinal) were not influenced by acemetacin. Like many non-steroidal anti-inflammatory compounds acemetacin inhibits also platelet aggregation. Motility of animals was lowered. In a granuloma pouch test a strong anti-inflammatory action was shown in vivo even without metabolic degradation of acemetacin. For the explanation of the anti-inflammatory action several mechanisms have to be taken into account.

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