Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the discovery that 3-(dimethylamino)-1,1-diphenyl-2-propanol hydrobromide (1) possesses potent reserpine-prevention activity in mice, a series of analogues of 1 was synthesized and evaluated as potential antidepressant agents. Several routes to analogues of 1 were evaluated, the most generally applicable of which was the regiospecific ring opening of a suitably functionalized 1,1-diaryl-2,3-epoxypropane (obtained in three stages from the corresponding benzophenone) with the appropriate amine. The more interesting compounds of the series were evaluated for their propensity to cause undesirable peripheral anticholinergic effects, all compounds tested being markedly less active than imipramine on this parameter. On the basis of its good activity in biochemical and pharmacological animal models of depression, together with its relative lack of anticholinergic side effects, 1-(3-chlorophenyl)-3-(dimethylamino)-1-phenyl-2-propanol hydrochloride (20, BRL 14342) was chosen for further evaluation.
 ...
PMID:Substituted 3-amino-1,1-diaryl-2-propanols as potential antidepressant agents. 53 85

In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT1B receptors mediate the monosynaptic reflex depression induced by exogenously applied 5-HT that was formed from the precursor L-5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by DL-p-chloroamphetamine, on spinal reflexes. DL-p-chloroamphetamine depressed the monosynaptic reflex and increased the polysynaptic reflex. The depletion of 5-HT abolished the monosynaptic reflex depression, but the increase in polysynaptic reflexes was maintained, suggesting that endogenous 5-HT released by DL-p-chloroamphetamine mediates depression of the monosynaptic reflex in the spinal cord. The depression of the monosynaptic reflex was antagonized by GR127935 (N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT1D receptor antagonist) but not by isamoltane (5-HT(1B) receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses monosynaptic reflex transmission via 5-HT1D receptors.
 ...
PMID:Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic reflex via 5-HT1D receptors. 1549 96