[Clinical and neurobiological aspects of long-term administration of psychotropic drugs].
In neuroleptic therapy for psychotic illnesses, clinical improvement occurs much later than central dopamine blockade, and its time course varies widely among patients. A hypothesis explaining neuroleptic-responsive illness cannot be explained by dopamine blockade alone. Nevertheless, experimental data suggest that this mechanism may be a step in the therapeutic process for schizophrenia. Explanations are suggested for the time lag in therapeutic response for neuroleptics, including the hypothesis of delayed inactivation of mid-brain dopamine neurones. Chronic benzodiazepine treatment elicits adaptive responses in the CNS that are manifested as functional tolerance and physical dependence. Possible mechanisms involved in such a profound alteration of neuronal functioning are suggested. Down regulation of benzodiazepine receptors has been shown to be related to functional tolerance under certain conditions. The effect of repeated treatment with antidepressants is compatible with the hypothesis that changes in central monoamine transmission are involved in the activity of these drugs. Beta-adrenergic receptors are desensitized and their density is decreased; alpha-2 adrenoreceptors sensitivity is reduced, and post-synaptic serotoninergic receptors sensitivity is increased. It remains to be clarified whether some of the changes have larger role than others or whether they all contribute to the psychotropic drug activity in the therapeutic process.
Département de pharmacologie, Faculté de médecine, Université de Nantes, France.
M
M
Bourin
J
J
Bradwejn
D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D017981:Receptors, Neurotransmitter; D001569:Benzodiazepines
Aspects cliniques et neurobiologiques de l'administration à long terme des psychotropes.