2. Academic Validation
  3. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells

Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells

  • Neurosci Lett. 2000 Jul 21;288(3):236-40. doi: 10.1016/s0304-3940(00)01225-8.
N L Zhukovskaya 1,  J F Neumaier
Affiliations

Affiliation

  • 1 Department of Psychiatry and Behavioral Sciences, Harborview Medical Center, University of Washington, Box 359911, 325 Ninth Avenue, Seattle, WA 98195, USA.
PMID: 10889351 DOI: 10.1016/s0304-3940(00)01225-8
Abstract

Clozapine is an atypical antipsychotic with high affinity for several serotonin receptors. This drug causes paradoxical downregulation of 5-hydroxytryptamine(2A) (5-HT)(2A) receptors, but its modulation of other serotonin receptors has not been studied. We examined the effects of clozapine and several other drugs on the regulation of rat 5-HT(6) and 5-HT(7) receptors individually expressed in transfected HeLa cells. Both 5-HT(6) and 5-HT(7) receptor densities (B(max)) were reduced by 5-carboxamidotryptamine, an agonist, and methiothepin, an inverse agonist. Clozapine reduced 5-HT(6) B(max). This suggests that 5-HT(6) receptors are also paradoxically downregulated by the antagonist clozapine. 5-Hydroxytryptamine(7) receptor B(max), on the other hand, was increased by clozapine. Clozapine's modulation of the 5-HT(6) and 5-HT(7) receptor levels may be important in the action of this atypical antipsychotic.

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