Typical Versus Atypical Antipsychotics; Occupation of Striatal Receptors and the Appearance of Extrapyramidal Symptomatology, in Healthy Volunteers

Summary

The purpose of this study is to determine in healthy volunteers treated with typical or atypical antipsychotics -AP-, the relationship between genetic polymorphisms in cytochrome genes CYP2D6 (\*3, \*4, \*5, \*6 and Nxn) and CYP3A5 (\*3) with antipsychotic pharmacokinetics, occupancy of striatal dopaminergic receptors and the appearance of extrapyramidal symptomatology -EPS-.

Timeline

Start

2011-02

Primary completion

2011-11

Completion

2011-12

Publications

• Background Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gasso P, Catalan R, Mateos JJ, Lomena F, Parellada E. Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr Res. 2007 Feb;90(1-3):115-22. doi: 10.1016/j.schres.2006.09.031. Epub 2006 Dec 5.
• Background Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gasso P, Deulofeu R, Mane A, Catalan R, Carne X. Polymorphism of dopamine D2 receptor (TaqIA, TaqIB, and-141C Ins/Del) and dopamine degradation enzyme (COMT G158A, A-278G) genes and extrapyramidal symptoms in patients with schizophrenia and bipolar disorders. Psychiatry Res. 2008 Nov 30;161(2):131-41. doi: 10.1016/j.psychres.2007.08.002. Epub 2008 Oct 15.
• Background Crescenti A, Mas S, Gasso P, Parellada E, Bernardo M, Lafuente A. Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal side-effects in patients receiving antipsychotic therapy. Clin Exp Pharmacol Physiol. 2008 Jul;35(7):807-11. doi: 10.1111/j.1440-1681.2008.04918.x. Epub 2008 Mar 12.
• Background Gasso P, Mas S, Bernardo M, Alvarez S, Parellada E, Lafuente A. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J. 2009 Dec;9(6):404-10. doi: 10.1038/tpj.2009.26. Epub 2009 Jun 9.
• Background Gasso P, Mas S, Crescenti A, Alvarez S, Parramon G, Garcia-Rizo C, Parellada E, Bernardo M, Lafuente A. Lack of association between antipsychotic-induced extrapyramidal symptoms and polymorphisms in dopamine metabolism and transport genes. Psychiatry Res. 2010 Jan 30;175(1-2):173-5. doi: 10.1016/j.psychres.2009.07.006. Epub 2009 Nov 5.
• Background Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007 Dec;116(3):496-526. doi: 10.1016/j.pharmthera.2007.09.004. Epub 2007 Oct 9.
• Background Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, De Gaspari IF, Bareggi SR. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet. 2007;46(5):359-88. doi: 10.2165/00003088-200746050-00001.
• Background Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008 Nov;392(6):1093-108. doi: 10.1007/s00216-008-2291-6. Epub 2008 Aug 10.
• Background Catafau AM, Penengo MM, Nucci G, Bullich S, Corripio I, Parellada E, Garcia-Ribera C, Gomeni R, Merlo-Pich E; Barcelona Clinical Imaging in Psychiatry Group. Pharmacokinetics and time-course of D(2) receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients. J Psychopharmacol. 2008 Nov;22(8):882-94. doi: 10.1177/0269881107083810. Epub 2008 Feb 28.
• Mas S, Gasso P, Fernandez de Bobadilla R, Arnaiz JA, Bernardo M, Lafuente A. Secondary nonmotor negative symptoms in healthy volunteers after single doses of haloperidol and risperidone: a double-blind, crossover, placebo-controlled trial. Hum Psychopharmacol. 2013 Nov;28(6):586-93. doi: 10.1002/hup.2350. Epub 2013 Oct 7.

Drugs

Indications

No indication recorded.