title: Fengabine, a novel antidepressant GABAergic agent. II. Effect on cerebral noradrenergic, serotonergic and GABAergic transmission in the rat.
abstract: The effects of fengabine (a novel benzylidene derivative possessing clinically demonstrated antidepressant action) on neurochemical parameters related to norepinephrine, serotonin and gamma-aminobutyric acid (GABA) neurons have been investigated in the rat and mouse brain. When given acutely, fengabine (50-1000 mg/kg i.p.) does not alter norepinephrine uptake but accelerates the turnover rate of norepinephrine in the rat brain as demonstrated by the enhancement of: the alpha-methyl-p-tyrosine-induced disappearance of norepinephrine in the hypothalamus; 3,4-dihydroxyphenylacetic acid levels in noradrenergic cell body areas; the pargyline-induced accumulation of normetanephrine in the hypothalamus; and 3,4-dihydroxyphenylethyleneglycol levels in the hypothalamus, septum and spinal cord. No tolerance to the effect of fengabine on the latter biochemical parameter was observed after repeated treatment for 2 weeks at doses of 100 or 200 mg/kg i.p., b.i.d. Fengabine (100 or 200 mg/kg i.p., b.i.d.), given for 14 days, causes a desensitization of isoprenaline-stimulated adenylate cyclase in septal and cortical slices of the rat but fails to modify cortical beta, alpha-1 or alpha-2 adrenoceptor binding sites. Fengabine (up to 400 mg/kg i.p.) has no effect on rat cerebral serotonin uptake, synthesis or metabolism. Moreover, when given subacutely (100 or 200 mg/kg i.p., b.i.d. for 2 weeks), it fails to alter rat cortical serotonine receptors or [3H]imipramine binding sites. Fengabine (up to 50-100 microM) is also inactive in vitro on [3H] GABA binding to GABAA or GABAB receptors in the rat brain or on GABA transaminase activity in the mouse brain.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002733:Chlorophenols / Q000494:pharmacology*; D003000:Clonidine / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007099:Imipramine / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D002733:Chlorophenols; D011963:Receptors, GABA-A; D012701:Serotonin; D013134:Spiperone; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; D004082:Dihydroalprenolol; D003000:Clonidine; D007099:Imipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D011224:Prazosin; C052028:fengabine