Actions of antipsychotic drugs on pancreatic β-cell function: Contrasting effects of clozapine and haloperidol

Leonard Best, Allen P. Yates, Gavin P. Reynolds

Research output: Contribution to journalArticlepeer-review

Abstract

The use of antipsychotic drugs is known to be associated with a number of adverse metabolic side effects, including diabetes mellitus. These side effects could be, at least in part, the result of impaired islet cell function, although the underlying mechanisms are unknown. We have studied the effects of the atypical antipsychotic clozapine and of the conventional drug haloperidol on electrical and secretory activity in rat pancreatic β-cells. At a low glucose concentration (4 mM), clozapine (5 μM) had little or no effect on membrane potential. However, at a stimulatory glucose concentration (16 mM), clozapine was found to hyperpolarize the cell membrane potential, resulting in a complete inhibition of electrical activity. In contrast, haloperidol (5 μM) was found to cause a marked depolarization of the membrane potential in the presence of both low and high concentrations of glucose. Clozapine and haloperidol were found, respectively, to increase and decrease β-cell input conductance, an index of K+ permeability. Single channel recordings indicated that changes in KATP channel activity contributed towards these effects. Neither clozapine nor haloperidol affected basal insulin release, although clozapine inhibited glucose-induced insulin release. It is concluded that clozapine and haloperidol exert contrasting actions on electrical activity in rat pancreatic β-cells as a result of opposing effects on K+ permeability. These findings may relate to the increased incidence of diabetes associated with clozapine treatment. © 2005 British Association for Psychopharmacology.
Original languageEnglish
Pages (from-to)597-601
Number of pages4
JournalJournal of Psychopharmacology
Volume19
Issue number6
DOIs
Publication statusPublished - Nov 2005

Keywords

  • Antipsychotic
  • Clozapine
  • Electrical activity
  • Haloperidol
  • Input conductance
  • Insulin release
  • KATP channel
  • Pancreatic β-cell

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