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 naive/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 naive/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.