RELATIVE PHARMACOLOGICAL EFFECTS OF 2-ALKYL-3,4-DIHYDROISOQUINOLINIUM CHLORIDES

¹ From The Burroughs Wellcome & Co. U.S.A. Experimental Research Laboratories, Tuckahoe, N. Y.

The chemical and pharmacological properties of three homologous series of 2-alkyl-3,4-dihydroisoquinolinium chlorides substituted in the 6 and 6,7 positions with hydroxy, methoxy and ethoxy groups have been studied. These 2-alkyl-3,4-dihydroisoquinolinium chlorides were of the same order of toxicity as the corresponding 2-alkyl-1,2,3,4-tetrahydroisoquinoline hydrochlorides.

Among the dihydroxy derivatives, lengthening of the carbon chain attached to the nitrogen converted the pure pressors into depressors. With the exception of the pressor 2-methyl-6,7-dimethoxy derivative (Lodal), the methoxy and ethoxy derivatives were predominantly depressors or biphasic depressor-pressors.

No evidence of tachyphylaxis was obtained.

Vagotomy had no effect on the pressors; it sensitized some of the depressors; and abolished the depressor phase of some of the mixed-acting compounds. Atropine usually had no effect.

The epinephrine response was usually enhanced by the pressors but unaffected by the other compounds.

The respiration and pulse rate were usually unaffected.

The dihydroxy derivatives stimulated the intestine while the remaining derivatives either stimulated or depressed. The rabbit and guinea pig uteri were stimulated by all the compounds.