The ability of DA agonists to activate orexin cells, particularly those in the medial LH/PFA, suggests that drugs that block DA receptors may also modulate the activity of orexin neurons. We were particularly interested in antipsychotic drugs (APDs) because treatment of schizophrenics with many of these drugs causes marked weight gain,19 leading to problems with patient compliance and inhibiting psychosocial integration, and because orexin potently produces feeding.20-22 All APDs have some D2 receptor affinity, although many of the APDs, particularly the newer generation (atypical) APDs, target many other receptors as well.23, 24
4.1. Effects Of Typical And Atypical Antipsychotic Drugs On Orexin Neurons.
We compared the effects of a panel of APDs, both typical and atypical, with different weight gain liabilities. Among these were several APDs with a high propensity for causing weight gain (e.g., clozapine), others that cause moderate weight gain (e.g., chlorpromazine), and some that do not elicit significant weight gain (e.g., haloperidol), as reported in a meta-analysis of weight change in schizophrenics six week after starting
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