demeclocycline and Bipolar-Disorder

The success of lithium in the treatment of manic-depressive illness has highlighted the problems posed by the minority of bipolar patients who are lithium nonresponders or who suffer severe adverse effects. A number of possible alternative treatments have been proposed, and the evidence in support of their clinical efficacy is evaluated. At this time, only the anticonvulsant carbamazepine can be regarded as a clinically applicable potential alternative to lithium. Further controlled studies are needed before the antimanic and prophylactic efficacy of carbamazepine can be regarded as conclusively established. Other treatment approaches are of considerable theoretical interest and of potential value clinically but need to be more thoroughly evaluated.

Topics: Ascorbic Acid; Bipolar Disorder; Bupropion; Carbamazepine; Choline; Clonazepam; Clonidine; Clorgyline; Demeclocycline; Fenfluramine; Humans; Methylene Blue; Phosphatidylcholines; Physostigmine; Propiophenones; Propranolol; Spironolactone; Thyroxine; Tryptophan; Valproic Acid

Lithium is a unique drug in its clinical profile in psychiatry. Lithium has numerous biochemical effects, but none has yet been proven to be its mode of therapeutic action. Inhibition of noradrenaline-sensitive adenylate cyclase is reviewed as the only biochemical effect of lithium shown to occur in both animals and man at therapeutic lithium concentrations. A tetracycline antibiotic, demeclocycline, also blocks noradrenaline-sensitive adenylate cyclase. A clinical trial of demeclocycline in mania would provide a test of the adenylate cyclase theory of lithium action.

Topics: Adenylyl Cyclase Inhibitors; Animals; Bipolar Disorder; Brain; Cyclic AMP; Demeclocycline; Dextroamphetamine; Epinephrine; Humans; Lithium; Motor Activity; Norepinephrine; Rats