Muscarinic cholinergic receptors in human narcolepsy: a PET study.
OBJECTIVE
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.


CONCLUSIONS
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.
Sudo
Y
Y
Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan. sudo_y@nirs.go.jp
Suhara
T
T
Honda
Y
Y
Nakajima
T
T
Okubo
Y
Y
Suzuki
K
K
Nakashima
Y
Y
Yoshikawa
K
K
Okauchi
T
T
Sasaki
Y
Y
Matsushita
M
M
D000328:Adult; D000818:Animals; D001561:Benzilates / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002491:Central Nervous System Agents / Q000097:blood / Q000627:therapeutic use; D004285:Dogs; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D009928:Organ Specificity; D010276:Parasympatholytics / Q000493:pharmacokinetics; D010880:Piperidines / Q000493:pharmacokinetics; D011976:Receptors, Muscarinic / Q000032:analysis*; D012016:Reference Values; D012044:Regression Analysis; D014055:Tomography, Emission-Computed
D001561:Benzilates; D002250:Carbon Radioisotopes; D002491:Central Nervous System Agents; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; C005101:mepenzolic acid