Evaluation of antidepressant activity of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a ß-substituted phenylethylamine in mice.

The ß-phenylethylamines are known to act as ligands for the trace amine receptors, a novel family of G-protein-coupled receptors. The trace amines are stored and released along with various neurotransmitter agents such as norepinephrine, serotonin, and dopamine and thus work as neuromodulator or neurotransmitter agents. Trace amines are known to play an important role in the pathophysiology of major depression. In our earlier study, we have demonstrated the synthesis of various ß-substituted phenylethylamine molecules hypothesized to be effective in various central nervous system disorders. The present study is an attempt to evaluate one of such molecules, 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol, in animal models of depression. Various behavioral paradigms of despair such as forced swim and tail-suspension tests were used to assess the antidepressant-like activity. Further, an alteration in the levels of various neurotransmitters (norepinephrine, serotonin, and dopamine) in the mouse brain following 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol administration was evaluated. The molecule (4-16 mg/kg., i.p.) dose-dependently inhibited the immobility period in mouse forced swim test, the effect comparable to venlafaxine. The ED50 values of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol and venlafaxine in mouse forced swim test were found to be 5.27 [4.38-6.35] mg/kg., i.p and 4.66 [3.48-6.25] mg/kg., i.p., respectively. Further, 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol at 4-16 mg/kg., i.p. reversed the immobility period in mouse tail-suspension test. Additionally, the molecule at 8 mg/kg., i.p. reversed reserpine-induced behavioral despair in mouse forced swim test. When administered simultaneously, it (4 and 8 mg/kg., i.p) enhanced the antidepressant activity of sub-effective doses of imipramine (2mg/kg., i.p.) or fluoxetine (2mg/kg., i.p.) in the mouse forced swim test. Neurochemical analysis revealed that the molecule at 8 mg/kg., i.p. increased the levels of norepinephrine (21% increase) without affecting serotonin in the mouse brain. However, at higher dose (16 mg/kg., i.p.), it increased the levels of norepinephrine (13% increase), serotonin (37% increase), and dopamine (42% increase). The molecule enhanced the locomotor activity in mice only at higher doses. The molecule, unlike venlafaxine, which potentiated barbiturate-induced hypnosis, was devoid of any sedative activity. In conclusion, 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol, possess antidepressant-like activity in animal models of depression by modulating the neurotransmitter levels in the brain. Such an activity might be due to the modulating action of this novel molecule on trace amine receptors. Such a molecule may be the future drugs of choice for the treatment of major depression.

Antibacterial activity of some newly synthesized azaphenanthrene and diazachrysene compounds.

Four newly synthesized azaphenanthrene compounds viz., 7,8,9,10-Tetrahydro-7-oxo-2-methoxy-benzo(c) phenathridine; 7,8,9,10-Tetrahydro -7-oxo-benzo(c) phenanthridine-2-[1-6-methoxy-1-naphthylimino)-methyl]cyclohexane-1,3-dione and 2-[1-(1-naphthyli; mino)-methyl]cyclohexane-1,3 dione and two diazachrysene compounds viz., 1,5-Diazachrysene and 2,5-Diazachrysese were screened for their antibacterial potency against a large number of bacterial strains. The antibacterial activity which to a varying degree was shown to be related to the aza, methoxy and keto groups, in the case of the Azaphenanthrene compounds, however, it was related to the position of the nitrogen atom in the ring in the case of Diazachrysene compounds.

Antibacterial effect of some azaphenanthrene compounds.

Five newly synthesized azaphenanthrene compounds have been studied for their antibacterial activity, which to varying degrees was shown to be related to the position of the aza, methyl, and benzyl groups in the ring.