Could the interaction of neuroleptics with calmodulin be an "explanation" of the psychotropic effects?
Calmodulin is a protein with calcium-dependent binding sites. Binding of calcium ions induces changes in the conformation and activation of many enzymes such as adenylate cyclase, guanylate cyclase, ATPase. Neuroleptic drugs bind calmodulin. Trifluoperazine has a very high affinity for calmodulin. Tricyclic antidepressants and benzodiazepines also bind calmodulin. Binding of neuroleptics inhibits many biological phenomena such as lymphocyte endocytosis, platelets aggregation. When neuroleptics are administrated chronically, calmodulin could act in regulation of the receptors specially in the drug induced supersensitivity of striatum dopamine receptors. These experiments about the regulation of the receptors mediated by calmodulin have been performed ten years ago and their results were not confirmed later. Moreover, binding of calmodulin is not specific of neuroleptic drugs. The effects of neuroleptics on calmodulin, only observed in vitro or with animals, seem to be mainly related to structural properties of the drugs.
Lejoyeux
M
M
Faculté de Médecine Saint-Antoine, Laboratoire de Biochimie, Paris.
Maziere
J C
JC
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D011954:Receptors, Dopamine / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D002147:Calmodulin; D011954:Receptors, Dopamine