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)

gamma-Aminobutyric acid (GABA) receptor agonists (e.g. progabide) are effective in behavioral tests predictive of antidepressant drug action. Also, these compounds, by changing the firing rate of the corresponding neurons, accelerate norepinephrine turnover (without changes in postsynaptic receptor density) and decrease 5-hydroxytryptamine (5-HT) liberation (with up-regulation of 5-HT2 receptors). At variance, tricyclic antidepressants block monoamine reuptake and cause down-regulation of beta-adrenergic and 5-HT2 receptors. Progabide exerts an antidepressant action which is indistinguishable from that of imipramine. The different modes of action of GABA receptor agonists and tricyclics, as well as alterations of GABA-related parameters by tricyclics, challenge the classical monoaminergic hypothesis of depression and suggest that GABA-mediated mechanisms play a role in this disorder.
 ...
PMID:Experimental basis for the antidepressant action of the GABA receptor agonist progabide. 608 56

Progabide, a new antiepileptic GABA agonist of moderate affinity for GABA receptors, has been studied in a number of psychiatric disorders and the results compared with the action of this drug in animal models. In an animal model for anxiety (the aversive response to periaqueductal grey stimulation in the rat) progabide had a similar action to that of diazepam. However in clinical trials to date the effect of the GABA agonist was inferior to that of benzodiazepines. As progabide diminishes both the nigrostriatal dopamine neuron activity and the effects of striatal dopamine receptor activation, a trial in schizophrenic patients was undertaken. Progabide was devoid of any evident antipsychotic action. However a certain improvement in responsiveness to the environment and in social interactions was noticed in hebephrenic and schizoaffective syndromes. This lack of antipsychotic effect of progabide may be a reflection of the weak activity of GABA agonists on limbic dopamine neurons. In these various clinical trials a definite improvement of affect and mood was noted in those patients receiving progabide. In clinical trials in depressed patients progabide produces a significant reduction in depressive symptoms, an action similar to that of imipramine both for the global clinical rating and the HRSD. This antidepressant activity is reflected by the action of progabide in behavioural models of depression such as olfactory bulbectomy, learned helplessness and the sleep-wake cycle.
 ...
PMID:The potential use of GABA agonists in psychiatric disorders: evidence from studies with progabide in animal models and clinical trials. 635 Nov 6