CANINE CATAPLEXY IS PREFERENTIALLY CONTROLLED BY ADRENERGIC-MECHANISMS - EVIDENCE USING MONOAMINE SELECTIVE UPTAKE INHIBITORS AND RELEASE ENHANCERS

Narcolepsy is currently treated with antidepressants to control REM-re lated symptoms such as cataplexy and with amphetamine-like stimulants for the management of sleepiness. Both stimulant and antidepressant dr ugs presynaptically enhance monoaminergic transmission but both classe s of compounds lack pharmacological specificity. In order to determine which monoamine is selectively involved in the therapeutic effect of these compounds, we examined the effects of selective monoamine uptake inhibitors and release enhancers on cataplexy using a canine model of the human disorder. A total of 14 compounds acting on the adrenergic (desipramine, nisoxetine, nortriptyline, tomoxetine, viloxazine), sero toninergic (fenfluramine, fluoxetine, indalpine, paroxetine, zimelidin e) and dopaminergic (amfonelic acid, amineptine, bupropion, GBR 12909) systems were tested. Some additional compounds interesting clinically but with less pharmacological selectivity, i.e., cocaine, dextroamphe tamine, methylphenidate, nomifensine and pemoline, were also included in the study. All compounds affecting noradrenergic transmission compl etely suppressed canine cataplexy at low doses in all dogs tested, whe reas compounds which predominantly modified serotoninergic and dopamin ergic transmission were either inactive or partially active at high do ses. Our results demonstrate the preferential involvement of adrenergi c systems in the control of cataplexy and, presumably, REM sleep atoni a. Our findings also demonstrate that canine narcolepsy is a useful to ol in assessing the pharmacological specificity of antidepressant drug s.