Cardiovascular and anticholinergic effects of zimelidine

Lindbom, L. O.; Malatray, J; Hall, Håkan; Ögren, Sven Ove

doi:10.1016/s0278-5846(82)80116-4

Cited by 5 publications

(3 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results indicate that zimelidine is a potent anticataplectic agent without noticeable effect on EDS. Zimelidine and its main metabolite norzimelidine are potent and selective 5-HT reuptake inhibitors both in vitro and in vivo (8,15). In our study, this action was shown by an 80% reduction of 5-HT bloodconcentration 24 h after an oral administration of 100 mg. On the other hand, zimelidine has no effect on peripheral or central cholinergic systems.…”

Section: Physiopathology Of Cataplexysupporting

confidence: 57%

“…In our study, this action was shown by an 80% reduction of 5-HT bloodconcentration 24 h after an oral administration of 100 mg. On the other hand, zimelidine has no effect on peripheral or central cholinergic systems. Studies done in vitro indicated low affinity of zimelidine to muscarinic receptors (15), and in vivo, zimelidine had no anticholinergic effect in animals or in humans treated for depression (9,15). Consequently, anticholinergic effect is not a prerequisite for a drug to exert anticataplectic action.…”

Section: Physiopathology Of Cataplexymentioning

confidence: 99%

See 1 more Smart Citation

Serotoninergic Reuptake Mechanisms in the Control of Cataplexy

Montplaisir

1986

Sleep

View full text Add to dashboard Cite

Summary: Zimelidine, a selective inhibitor of serotonin (5-HT) reuptake in the CNS, was administered to narcoleptic patients. This medication has a potent anticataplectic action without improving daytime somnolence. These results suggest that 5-HT neuronal systems are involved in the physiopathology of cataplexy. Zimelidine, however, has no anticholinergic effect, so it is unlikely that cholinergic mechanisms thought to be important in animal cataplexy would playa major role in human cataplexy. In addition, zimelidine had no effect on nocturnal sleep patterns of these patients which is surprising considering the importance of 5-HT neuronal systems in sleep physiology. A 5-HT hypothesis of cataplexy is formulated, and the mechanisms of action of other anticataplectic agents are discussed.Key Words: Narcolepsy-Cataplexy-Serotonin-Zimelidine-Myoclonus.Narcoleptic patients complain of two major symptoms, namely, excessive daytime sleepiness (EDS) and cataplexy. Clinical data suggest that different mechanisms are involved in these two symptoms. In most patients, EDS and cataplexy do not develop simultaneously, and there is no correlation between the intensity of the two symptoms. Pharmacological studies also suggest that different mechanisms are involved. For instance, drugs known to improve EDS have little or no effect on cataplexy, and, conversely, most anticataplectic medications do not relieve the complaint of EDS (1).In humans, EDS most likely involves dopaminergic mechanisms in the central nervous system (CNS). For instance, low concentrations of free dopamine (DA) (2) and of homovanillic acid (HVA) (3), the main metabolite of DA, were found in the cerebrospinal fluid (CSF) of narcoleptic patients. In addition, psychostimulants effective to treat daytime sleepiness selectively decrease DA reuptake (4).The pathophysiology of cataplexy is more controversial. In humans, most data come from pharmacological studies (5). Although there is no controlled study comparing the potency of various anticataplectic agents, our clinical experience indicates that chlorimipramine is the most effective medication. Among anticataplectic agents, chlorimipramine also happens to be the most potent 5-HT reuptake blocker (6). We hypothesize that this mechanism is responsible for the anticataplectic action of this medication. However, chlorimipramine has also a strong anticholinergic action, and desmethylchlorimipramine, its main metabolite, is a norepinephrine (NE) reuptake blocker in the CNS. The anticholinergic

show abstract

Section: Physiopathology Of Cataplexysupporting

confidence: 57%

Section: Physiopathology Of Cataplexymentioning

confidence: 99%

Serotoninergic Reuptake Mechanisms in the Control of Cataplexy

Montplaisir

1986

Sleep

View full text Add to dashboard Cite

show abstract

“…19 Equivalent results have been described in other studies. 18,[20][21][22][23] However, results of these studies may not be directly relevant to the clinical use of clomipramine, because the drug was administered intravenously. Intravenous administration leads to initially higher plasma concentrations of clomipramine, compared with oral administration.…”

Section: Discussionmentioning

confidence: 99%