PHARMACOLOGICAL ASPECTS OF HUMAN AND CANINE NARCOLEPSY
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Abstract
Narcolepsy-cataplexy is a disabling neurological disorder that affects individuals. The main clinical features of narcolepsy, excessive daytime sleepiness and symptoms of abnormal REM sleep (cataplexy, sleep paralysis, hypnagogic hallucinations) are currently treated using amphetamine-like compounds or modafinil and antidepressants. Pharmacological research in the area is facilitated greatly by the existence of a canine model of the disorder. The mode of action of these compounds involves presynaptic activation of adrenergic transmission for the anticataplectic effects of antidepressant compounds and presynaptic activation of dopaminergic transmission for the EEG arousal effects of amphetamine-like stimulants. The mode of action of modafinil is still uncertain, and other neurochemical systems may offer interesting avenues for therapeutic development. Pharmacological and physiological studies using the canine model have identified primary neurochemical and neuroanatomical systems that underlie the expression of abnormal REM sleep and excessive sleepiness in narcolepsy. These involve mostly the pontine and basal forebrain cholinergic, the pontine adrenergic and the mesolimbic and mesocortical dopaminergic systems. These studies confirm a continuing need for basic research in both human and canine narcolepsy, and new treatments that act directly at the level of the primary defect in narcolepsy might be forthcoming. © 1997 Elsevier Science Ltd. All rights reserved
Abbreviations
CNSCentral nervous system –
DATDopamine transporter –
EEGElectroencephalogram –
FECTFood-elicited cataplexy test –
GABAGamma-aminobutyric acid –
GHBGamma-hydroxybutyrate –
HLAHuman leukocyte antigen –
5HT5-Hydroxytryptamine (serotonin) –
LDTLateral dorsal tegmentum –
MAOIMonoamine oxidase inhibitor
MSLTMultiple sleep latency test –
MWTMaintenance of wakefulness test –
NETNorepinephrine transporter –
PPTPedunculopontine tegmentum –
PRFPontine reticular formation –
REM sleepRapid eye movement sleep –
SOREMPSleep onset REM period –
TRHThyrotropin-releasing hormone –
VTAVentral tegmental area;
Copyright © 1997 Elsevier Science Ltd. All rights reserved.