Measurement of the serotonin 1A receptor availability in patients with schizophrenia during treatment with the antipsychotic medication ziprasidone.

Abstract

The aim of this study was to compare 5-HT(1A) availability in vivo in individuals with schizophrenia before and during treatment with the atypical antipsychotic ziprasidone. Six individuals with schizophrenia underwent two PET scans with [(11)C]WAY 100635; the first while medication-free (baseline) and the second while taking the atypical antipsychotic ziprasidone (on-medication). Regional volumes of distribution (V(T), mL g(-1)) were derived using a two-tissue compartment kinetic model. Outcome measures included binding potential relative to the plasma (BP(P), mL g(-1)) and the binding potential relative to the nonspecific distribution volume (BP(ND), unitless). No significant differences were observed in regional BP(P) or BP(ND) with ziprasidone treatment. A significant correlation was noted between BP(P) measured in the orbitofrontal cortex during the on-medication condition and degree of improvement in negative symptoms with treatment (r = 0.96, p = 0.004). Consistent with the published literature of changes in 5-HT(1A) binding during treatment with 5-HT(1A) receptor agonists, this study did not detect a significant reduction in 5-HT(1A) binding with ziprasidone. The finding of a relationship between 5-HT(1A) binding and the degree of improvement in negative symptoms provides further support for the role of the 5-HT(1A) receptor in the pathophysiology and treatment of this symptom domain.

• Authors: W Gordon Frankle, Ilise Lombardo, Lawrence S Kegeles, Mark Slifstein, John H Martin, Yiyun Huang, Dah-Ren Hwang, Elisa Reich, Claudine Cangiano, Roberto Gil, Anissa Abi-Dargham, Marc Laruelle
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 25 Issue 6 Pg. 734-43 (Jun 2011) ISSN: 1461-7285 [Electronic] United States
• PMID: 21109614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Carbon Radioisotopes
• Piperazines
• Pyridines
• Serotonin Antagonists
• Thiazoles
• Receptor, Serotonin, 5-HT1A
• ziprasidone
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide

Topics

• Adult
• Antipsychotic Agents (pharmacology, therapeutic use)
• Brain (drug effects, metabolism)
• Carbon Radioisotopes
• Female
• Humans
• Magnetic Resonance Imaging (methods)
• Male
• Piperazines (pharmacology, therapeutic use)
• Positron-Emission Tomography (methods)
• Psychiatric Status Rating Scales
• Pyridines
• Radioligand Assay (methods)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Schizophrenia (diagnosis, drug therapy, metabolism)
• Serotonin Antagonists
• Thiazoles (pharmacology, therapeutic use)