[On the pharmacology of 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335), a histamine and serotonin antagonist (author's transl)]

Abstract

The substance 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335) was examined for its antagonistic effects against histamine and serotonin, for its atropine-like properties as well as for a series of other qualities in comparison with cyproheptadine and pimethixene. The anti-histamine and anti-serotonin activities of compound WA 335 on the smooth muscle and the capillary do not only exceed that of cyproheptadine but also that of pimethixene. WA 335 shows an extremely strong binding to histamine and serotonin receptors. In the dose range in which it causes already an antamine effect, its oral absorption is very good. The anti-anaphylactic effect is much stronger than that of cyproheptadine. Like pimethixene and cyproheptadine, WA 335 has no distinct antagonistic qualities against bradykinin. The anticholinergic effects of WA 335 are dependent on the test object. In examinations on the bronchus of the guinea pig and the pupil of the mouse, the atropine-like efficiency corresponds to that of cyproheptadine; it is stronger on the stimulated vagus of the cat and less efficient than cyproheptadine on the stomach of the rat. WA 335 has distinct central atropine-like properties. It possesses a strong surface anesthetic activity. The effects of WA 335 on circulation are dependent on species. In contrast to pimethixene, compound WA 335 like cyproheptadine potentiates the effects of norepinephrine in cats. The reduction of the carotid sinus reflex in the cat is more distinct after WA 335 than after pimethixene and corresponds to that produced by cyproheptadine. Higher doses of WA 335 than are necessary to demonstrate antaminic effects are needed to provoke central nervous effects. WA 335 shows no analgesic potency in mice. The influence on body temperature in the rat is similar to that of cyproheptadine. WA 335 is equally efficient as pimethixene with regard to the inhibition of spontaneous motility and prolongation of barbiturate sleep in mice, and shows the same anti-emetic activity as does chlorpromazine in dogs. In contrast to chlorpromazine the behaviour of dogs and cats is distinctly altered already by doses of WA 335 which cause a slight sedation.