The neurochemistry of mania. The effect of lithium on catecholamines, indoleamines and calcium mobilization.

In an attempt to elucidate the chemical pathology of mania one has to consider the pharmacology of the two most effective treatments for this illness: lithium and the neuroleptics. Some of the possible mechanisms of action of these drugs on catecholamine and indoleamine mechanisms are discussed. The majority of this article is based on my and my colleagues' work which has been carried out in this MRC Laboratory on the effect of lithium on biological variates in bipolar patients and the effects of the administration of antidepressant treatments in these patients. It is concluded that lithium has a similar action on these mechanisms in both unipolar and bipolar patients which might suggest a common pathology in both unipolar and bipolar illness. It is suggested that in order to maintain an euthymic state in a bipolar patient one should maintain a certain degree of sensitivity of 5-HT2 receptors. This sensitivity may be related to the activity of calcium channels and to the polyphosphoinositide system. The former system can be regulated by the administration of calcium channel antagonists which have been shown to be effective in the treatment of mania. The polyphosphoinositide system is one that can be regulated by therapeutic concentrations of lithium. It is concluded that co-administration of a calcium channel antagonist and lithium may be a very effective treatment for mania.