Unique Effects of Clozapine: A Pharmacological Perspective.

Autor:	Khokhar JY; Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Dartmouth Clinical and Translational Science Institute, Dartmouth College, Hanover, NH, United States., Henricks AM; Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Dartmouth Clinical and Translational Science Institute, Dartmouth College, Hanover, NH, United States., Sullivan EDK; Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Dartmouth Clinical and Translational Science Institute, Dartmouth College, Hanover, NH, United States., Green AI; Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Dartmouth Clinical and Translational Science Institute, Dartmouth College, Hanover, NH, United States. Electronic address: alan.i.green@dartmouth.edu.
Jazyk:	angličtina
Zdroj:	Advances in pharmacology (San Diego, Calif.) [Adv Pharmacol] 2018; Vol. 82, pp. 137-162. Date of Electronic Publication: 2018 Jan 12.
DOI:	10.1016/bs.apha.2017.09.009
Abstrakt:	Schizophrenia is a heterogenous and severe neuropsychiatric disorder that affects nearly 1% of the population worldwide. Antipsychotic drugs are the mainstay of treatment, but not all patients with schizophrenia respond to treatment with these agents. Clozapine, the first atypical antipsychotic, is a highly effective medication for patients with schizophrenia who do not respond to other antipsychotics. Although clozapine tends not to produce extrapyramidal symptoms, other side effects of the drug (e.g., agranulocytosis, myocarditis, seizures) limit its widespread use. This chapter reviews clozapine's unique clinical effects and unusual pharmacological profile. In addition to its effects in treatment-resistant schizophrenia, clozapine has been shown to decrease suicidality, which occurs at an increased rate in patients with schizophrenia. Still preliminary, but consistent data, also suggest that clozapine limits substance use in these patients, an important effect since substance use disorders are common in patients with schizophrenia and are associated with a poor outcome, including an increased risk for suicide and poor response to treatment. We have suggested, from animal studies, that clozapine's apparent ability to limit substance use may occur through its actions as a weak dopamine D2 receptor antagonist, a potent norepinephrine α-2 receptor antagonist and a norepinephrine reuptake inhibitor. Using animal models, we have built combinations of agents toward creation of safer clozapine-like drugs to reduce substance use in these patients. Future research into the mechanisms of action of clozapine toward the development of safe clozapine-like agents is of great public health importance. (© 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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