Monoaminergic mechanisms and experimental cataplexy

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Abstract
The effects of pharmacological alteration of the monoamine systems were investigated in a canine model of narcolepsy. Cataplexy was quantified in eight severely affected dogs by means of the food‐elicited cataplexy test. The specific norepinephrine (NE) uptake blocker nisoxetine, and (to a much lesser extent) the specific serotonin (5‐HT) uptake blocker fluoxetine, significantly suppressed cataplexy, as did the tricy'lic antidepressants protriptyline, amitriptyline, and chlorimipramine. Thus, experimental cataplexy is suppressed more by inhibition of the uptake of NE than of 5‐HT. Methylphenidate, the α‐adrenoreceptor blocker clonidine, and the dopamine receptor blocker pimozide also suppressed cataplexy in dogs. The β‐adrenergic blocker propranolol, the fatty acid γ‐hydroxybutyrate, and the monoamine oxidase inhibitors clorgyline and pargyline had little or no effect. With one exception (pimozide). all the drugs that suppressed cataplexy are known to be potent suppressors of REM sleep. The suppression of cataplexy induced by nisoxetine or protriptyline was reversed by the anticholinesterase physostigmine, further supporting a postulated aminergic‐cholinergic interaction in the mechanisms for cataplexy.