Monoaminergic mechanisms and experimental cataplexy.
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 tricyclic antidepressants protriptyline, amitriptyline, and chlorimipramine. Thus, experimental cataplexy is suppressed more by inhibition of the uptake of NE than of 5-HT. Methylphenidate, the alpha-adrenoreceptor blocker clonidine, and the dopamine receptor blocker pimozide also suppressed cataplexy in dogs. The beta-adrenergic blocker propranolol, the fatty acid gamma-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.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001679:Biogenic Amines / Q000502:physiology*; D002385:Cataplexy / Q000188:drug therapy / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D010830:Physostigmine / Q000008:administration & dosage; D010868:Pimozide / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D012895:Sleep, REM / Q000502:physiology*; D012978:Sodium Oxybate / Q000627:therapeutic use
D000929:Antidepressive Agents, Tricyclic; D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; D005473:Fluoxetine; C011386:nisoxetine; D010868:Pimozide; D008774:Methylphenidate; D012978:Sodium Oxybate; D010830:Physostigmine; D011433:Propranolol; D006220:Haloperidol