Monophenolic octahydrobenzo[f]quinolines: central dopamine- and serotonin-receptor stimulating activity

Abstract

Eight monophenolic cis- and trans-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines were synthesized and tested for central dopamine- and serotonin-receptor stimulating activity, using biochemical and behavioral tests in rats. The trans-7-, -8-, and -9-hydroxy isomers all elicited central pre- and postsynaptic dopaminergic receptor stimulation, while the trans-10-hydroxy isomer was devoid of dopaminergic activity but instead showed central serotoninergic activity. In all 4 isomeric pairs, the trans isomers were consistently much more potent than their corresponding cis analog. The apparent presynaptic selectivity of the dopaminergic cis isomer cis-9-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline could not be confirmed due to the toxic properties of this compound. Central dopamine receptors (autoreceptors and postsynaptic receptors) can accept dopaminergic compounds with 1 of possibly 2 N-substituents being larger than n-propyl, if this substituent is properly oriented in relation to the rest of the molecule.