Muscarinic cholinergic receptors in human narcolepsy

Objectives: To investigate the function of the muscarinic cholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchRs. Background: Muscarinic neural transmission serves as the main executive system in REM sleep. Studies in canine narcolepsy reported an increase in mAchRs in the pons. Methods: The mAchRs of 11 drug naïve/free patients with narcolepsy and 21 normal controls were investigated using PET with [11C] N-methyl-4-piperidylbenzilate ([11C]NMPB). Measurements were done in the pons, thalamus, striatum, and cerebral cortex. Seven of the 11 patients also underwent additional PET scans after the alleviation of symptoms by pharmacotherapy. Results: There were no differences in [11C]NMPB binding between the control and drug naïve/free patients in all areas analyzed. At the time of on-medication PET scan, [11C]NMPB binding in the thalamus was decreased, but only to a small degree compared with that by anticholinergic drugs. Conclusion: The present results do not support the notion that the mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy.

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