The norepinephrine reuptake inhibitor reboxetine is more potent in treating murine narcoleptic episodes than the serotonin reuptake inhibitor escitalopram
| Autor: | Markus Fendt, Judith Leibiger, Christian Schmidt |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Time Factors Cataplexy Serotonin reuptake inhibitor Morpholines Mice Transgenic Pharmacology Citalopram 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice Reboxetine 0302 clinical medicine Norepinephrine reuptake inhibitor Internal medicine medicine Escitalopram Animals Narcolepsy Orexins biology Adrenergic Uptake Inhibitors Dose-Response Relationship Drug business.industry Electromyography Electroencephalography medicine.disease Cirazoline Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Norepinephrine transporter chemistry biology.protein medicine.symptom business 030217 neurology & neurosurgery Locomotion Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Behavioural brain research. 308 |
| ISSN: | 1872-7549 |
| Popis: | One of the major symptoms of narcolepsy is cataplexy, a sudden loss of muscle tone. Despite the advances in understanding the neuropathology of narcolepsy, cataplexy is still treated symptomatically with antidepressants. Here, we investigate in a murine narcolepsy model the hypothesis that the antidepressants specifically blocking norepinephrine reuptake are more potent in treating narcoleptic episodes than the antidepressants blocking of serotonin reuptake. Furthermore, we tested the effects of α1 receptor stimulation and blockade, respectively, on narcoleptic episodes. Orexin-deficient mice were treated with different doses of the norepinephrine reuptake inhibitor reboxetine, the serotonin reuptake inhibitor escitalopram, the α1 receptor agonist cirazoline or the α1 receptor antagonist prazosin. The effect of these treatments on narcoleptic episodes was tested. Additionally, potential treatment effects on locomotor activity in an open-field were tested. Reboxetine (doses ≥0.55mg/kg) as well as escitalopram (doses ≥3.0mg/kg) dose-dependently reduced the number of narcoleptic episodes in orexin-deficient mice. The ED50 for reboxetine (0.012mg/kg) was significantly lower than for escitalopram (0.44mg/kg). Cirazoline and prazosin did not affect narcoleptic episodes. Furthermore, cirazoline but not the other compounds reduced locomotor activity of the mice. The present study strongly supports the hypothesis that a specific blockade of norepinephrine reuptake is more potent in treating cataplexy than a specific blockade of serotonin reuptake. This argues for the development of more specific norepinephrine reuptake inhibitors for the treatment of narcolepsy. |
| Databáze: | OpenAIRE |
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