Interaction of lithium with 5-HT(1B) receptors in depressed unipolar patients treated with clomipramine and lithium versus clomipramine and placebo: preliminary results.
Lithium is commonly used in combination with antidepressant drugs as a treatment for refractory depression; less often, it is used in non-resistant depression. The aim of this study was to examine the interaction of lithium with 5-HT(1B) receptors in 10 non-resistant unipolar depressed patients treated with clomipramine+lithium (C+L) vs. clomipramine+placebo (C+P). A mediation of the serotonergic system has been proposed in the literature to explain the clinical effect of lithium. Indeed, in a previous study of healthy human blood platelets, we demonstrated the interaction of lithium with adenylate cyclase activity coupled to 5-HT(1B) receptors. The functional activity of these receptors was measured by studying the inhibitory effect of L694,247, a 5-HT(1B) receptor agonist, on the adenylate cyclase activity determined by the production of cAMP. Using the same technique in the present study, we found that lithium significantly reduced the inhibition of adenylate cyclase activity induced by 5-HT(1B) receptor activation. This result confirms the specific interaction of lithium with 5-HT(1B) receptors. Moreover, a correlation between the percentage of 5-HT(1B) receptor-dependent adenylate cyclase inhibition and the clinical benefit of lithium was established, suggesting 5-HT(1B) receptors may be a target for the therapeutic effect of lithium.
Januel
Dominique
D
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France. djanuel@freesurf.fr
Massot
Olivier
O
Poirier
Marie-France
MF
Olié
Jean-Pierre
JP
Fillion
Gilles
G
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000201:enzymology; D002997:Clomipramine / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
D000067956:Adenylyl Cyclase Inhibitors; D000928:Antidepressive Agents; C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D016651:Lithium Carbonate; D000262:Adenylyl Cyclases; D002997:Clomipramine