Fengabine, a New GABAmimetic Agent in the Treatment of Depressive Disorders: An Overview of Six Double-Blind Studies versus Tricyclics

Abstract

Fengabine is a new GABAmimetic compound active in animal models predictive of antidepressant activity. The present overview reports the results of 6 double-blind trials versus tricyclics (TCAs) (3 in outpatients and 3 in inpatients). Overall, 398 adult patients (149 males and 249 females) were treated; 194 with fengabine and 204 with TCAs (98 clomipramine, 63 amitriptyline and 43 imipramine). 284 suffered from major depression (MD) (including major depressive disorder and bipolar disorder, depressed; DSM III) and 114 from minor depression (MiD) including dysthymic disorder, atypical depression and adjustment disorder with depressive mood (DSM III). Dosage ranged from 600 to 2,400 mg/day for fengabine and 50 to 200 mg/day for TCAs. Efficacy was evaluated with the HAM-D scale. 311 subjects (154 fengabine and 157 TCAs) ended the 4-week treatment period. Considering the whole sample and mean 1AM-D scores, no significant differences emerged between the 2 treatment groups at any of the assessment periods. Because of a significant treatment × type of depression interaction, MD and MiD were analysed separately, and a different trend appeared in the 2 subgroups with TCAs behaving slightly better than fengabine in MD and fengabine performing slightly better than TCAs in MiD. Using the physician’s clinical improvement, 74% of patients under fengabine and 72% of those under TCAs were rated as improved or much improved. Side effects, particularly of the anticholinergic type were significantly more frequent in the TCAs group. Gamma-GT were more frequently altered in the fengabine group (30.4 vs. 10.5%); this increase was interpreted as a consequence of enzymatic induction. Lastly, more patients taking fengabine exhibited an increase in cholesterol values.

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

“…Increased GABA A /benzodiazepine binding sites were also documented, implying that the decreased GABA activity caused the binding sites to be increased as an outcome of an adaptive mechanism [5,6]. It is also well-known that GABA agonists have anti-depressant effects [7,8].…”

Fengabine in depression: A placebo‐controlled study of a GABA agonist

“…Improvement on fengabine has been reported in a number of open studies (Musch, 1986) with some suggestion of early response. Several double-blind comparisons with tricyclic antidepressants have not shown significant differences up to 4 weeks (Magni et al, 1988;Morselli et al, 1989). No placebo-controlled study of either drug has been reported.…”

“…Initial pharmacokinetic studies showed it to be well tolerated in doses up to 1200 mg daily. Several open studies, one doubleblind comparison with tricyclics, have suggested that it is an antidepressant in humans (Musch, 1986;Magni et al, 1988;Morselli et al, 1989). However, open studies can provide only preliminary suggestive data, and no placebo-controlled trials of GABA agonists in depression have so far been reported.…”

Biological Properties of Schiff Bases and Azo Derivatives of Phenols

“…(Scheme 20) [195][196]. Fengabine (239) is also a Schiff base and acts as an [121,168] 216 [121,168] 217 [121,168] 222 [163] 223 [163] 218 [163] 224 [163] 225 [163] 219 [163] O O S NH [197][198][199][200].…”