61. Muscarinic Acetylcholinergic Receptors in Human Narcolepsy: A Positron Emission Tomography Study

Yasuhiko Sudo, Tetsuya Suhara, Yutaka Honda, Toru. Nakajima, Yoshiro Okubo, Kazutoshi Suzuki, Yoshifumi Nakashima, Kyosan Yoshikawa, Takashi Okauchi, Yasuhito Sasaki, and Masaaki Matsushita

Keywords: [¹¹C]NMPB, muscarinic receptors, narcolepsy, clomiplamine

Objective: To investigate the function of the muscarinic acetylcholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchR.
Background: Muscarinic neural transmission serves as the main executive system in rapid eye movement (REM) sleep. Studies in canine narcolepsy reported an increase in mAchR in the pons.

Methods: mAchR of 11 drug naïve/free patients with narcolepsy and 21 normal controls were investigated using positron emission tomography (PET) with [¹¹C]N-methyl-4-piperidylbenzilate (NMPB). Measurements were done in the pons, thalamus, striatum and cerebral cortex. Seven of the 11 patients also underwent an additional PET scan 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 inhibited, but only to a small degree compared with that by anticholinergic drugs.

Conclusion: The present results do not support the notion that mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy.

Publications:
Sudo, Y., et al.: Neurology, 51:1297-1302, 1998.