Impact of schizophrenia and chronic antipsychotic treatment on [123I]CNS-1261 binding to N-methyl-D-aspartate receptors in vivo.

Abstract

BACKGROUND:

Antipsychotic drugs modulate N-methyl-D-aspartate (NMDA) receptor function in animals. The novel single photon emission tomography (SPET) radiotracer [123I]CNS-1261 binds to the PCP/MK-801 intrachannel site of the NMDA receptor, allowing the noninvasive estimation of NMDA receptor activity in living humans. We used [123I]CNS-1261 to determine whether binding to the NMDA receptor intrachannel PCP/MK-801 site is affected by schizophrenia or by treatment with typical antipsychotics and clozapine in vivo.

METHODS:

Three groups of schizophrenia patients were recruited-drug free (n = 5), typical antipsychotic treated (n = 7), and clozapine treated (n = 9)-as well as a control group of healthy normal volunteers (n = 13). All underwent [123I]CNS-1261 SPET scanning. Total volume of distribution of [123I]CNS-1261 was determined within predefined user-independent regions of interest after alignment of all images to a common template.

RESULTS:

There was no apparent difference in total volume of distribution of [123I]CNS-1261 in drug-free patients relative to healthy control subjects. A nonsignificant reduction in total volume of distribution was observed in typical antipsychotic treated patients. A significant decline in total volume of distribution of [123I]CNS-1261 was observed in all examined brain regions in the clozapine-treated patient group relative to healthy control subjects (p < .005).

CONCLUSIONS:

Clozapine treatment resulted in a global reduction in [123I]CNS-1261 binding to the NMDA receptor intrachannel PCP/MK-801 site in vivo. This supports an effect of the drug on glutamatergic systems that could be exploited for future antipsychotic drug discovery.

• Authors: Rodrigo A Bressan, Kjell Erlandsson, James M Stone, Rachel S Mulligan, John H Krystal, Peter J Ell, Lyn S Pilowsky
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 58 Issue 1 Pg. 41-6 (Jul 01 2005) ISSN: 0006-3223 [Print] United States
• PMID: 15992521 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antipsychotic Agents
• CNS 1261
• Guanidines
• Iodine Radioisotopes
• Receptors, N-Methyl-D-Aspartate
• Clozapine

Topics

• Adult
• Antipsychotic Agents (pharmacology, therapeutic use)
• Clozapine (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Guanidines (metabolism)
• Humans
• Iodine Radioisotopes (metabolism)
• Male
• Receptors, N-Methyl-D-Aspartate (drug effects, metabolism, physiology)
• Schizophrenia (diagnostic imaging, drug therapy, physiopathology)
• Tomography, Emission-Computed, Single-Photon