CERTAIN INHIBITORY PROPERTIES POSSESSED BY A HOMOLOGOUS SERIES OF p-n-ALKYLOXYPHENYLETHYLAMINES

¹ From the Department of Pharmacology and Therapeutics, University of Sheffield, and the Pharmacological Department, Boots Pure Drug Co. Ltd., Nottingham

1. Eight members of a homologous series of p-n-alkyloxyphenylethylamines have been examined and found to inhibit the action of certain drugs both on isolated smooth muscle and in the intact animal.

2. This inhibitory action has been studied on excised uteri from the rabbit, guinea pig, cat and rat and on the excised intestine from the rabbit.

It has been shown that the presence of a member of the p-n-alkyloxyphenylethylamine series in the isolated organ bath inhibits the action on smooth muscle of all the substances examined which produce a contraction of smooth muscle. The behaviour of these substances in relation to adrenaline is peculiar in that they inhibit its action on the uterus of the rabbit, where it causes the muscle to contract, but have no action on the uterus of the cat, guinea pig and rat, which are relaxed by adrenaline.

3. It is demonstrated that this inhibitory activity increases with increase in the length of the alkyloxy side chain until peak activity is reached with the hexoxy derivative after which a decline in activity occurs.

4. It is also shown that tyramine, as well as its alkyl ethers, can render isolated smooth muscle insensitive to the action of drugs which normally produce a contraction, but in the concentrations used in these experiments, tyramine fails to inhibit the action of adrenaline on tissues which respond by relaxation.

5. The inhibitory action of members of the alkyloxy series on smooth muscle is only observed on isolated tissue and their injection into the intact animal fails to influence the response of the uterus and intestine in situ to smooth muscle stimulants.

6. Members of the alkyloxy series inhibit the action of the vagus and acetyl choline on the heart, although they do not affect the peripheral vasodilatation caused by acetyl choline.

7. In the intact rabbit the members of the alkyloxy series sensitize the animal to the action of adrenaline. This effect soon passes off, and is sometimes followed by a period of reduced sensitivity. These substances do not sensitize the cat to adrenaline although the period of reduced sensitivity to adrenaline already referred to in the case of the rabbit, is also frequently seen with the cat.

8. The mechanism of the inhibitory action of the p-n-alkyloxyphenylethylamine on smooth muscle is discussed.