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  • Title: Dopaminergic activity of cis-trans isomers of benzhydro[f]quinoline analogs.
    Author: Verimer T, Long JP, Rusterholz DR, Flynn JR, Cannon JG, Lee T.
    Journal: Eur J Pharmacol; 1980 Jun 27; 64(4):271-7. PubMed ID: 7389823.
    Abstract:
    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.
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