Dopaminergic activity of cis-trans isomers of benzhydro[f]quinoline analogs.
A comparison of the biological activity of isomers with varying alkyl substitutions on the heterocyclic nitrogen of benzhydro[f]quinoline derivatives was made. The secondary amines did not inhibit adrenergic transmission. The trans-isomer of the secondary amine was 0.5 as active as norepinephrine when evaluated for positive chronotropic action in anesthetized cats. The trans-isomers of the N-alkyl derivatives produce inhibition of responses produced by stimulation of cardioaccelerator nerves with doses of 1--5 mumol/kg. Likewise potent emetic activity (dog) and rotational behavior (rat) was observed with the N-alkyl derivatives when administered subcutaneously. The cis-isomers were much less active. The neuronal inhibitions in cats were antagonized by haloperidol 100 micrograms/kg, except the cis-isomer of the N-ethyl derivate which required phentolamine, 2 mg/kg. In general, the transisomers were more potent in contracting the isolated rabbit aorta. This response appeared to be mediated through an alpha-adrenergic mechanism since phentolamine blocked these responses. The trans-isomer TL-305 was effective in relaxing methacholine contracted guinea-pig trachea through a beta-adrenergic mechanism since propranolol blocked this response.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004285:Dogs; D004639:Emetics / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D012399:Rotation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D004639:Emetics; D011804:Quinolines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D006220:Haloperidol; D010646:Phentolamine