Don't have a clue how they'd have patent protection for this molecule. Use patent, I guess. Trial was supposed to launch 4Q18, but no record of it to date? Perhaps those at CT.gov are subject to furlough, and it has launched.
Behav Brain Res. 2016 Jul 15;308:205-10. doi: 10.1016/j.bbr.2016.04.033. Epub 2016 Apr 23.
The norepinephrine reuptake inhibitor reboxetine is more potent in treating murine narcoleptic episodes than the serotonin reuptake inhibitor escitalopram.
Schmidt C1, Leibiger J2, Fendt M3.
1
Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany.
2
Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany; Integrative Neuroscience Program, Otto-von-Guericke University Magdeburg, Germany.
3
Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany; Center of Behavioral Brain Sciences, Magdeburg, Germany. Electronic address: markus.fendt@med.ovgu.de.
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 a1 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 a1 receptor agonist cirazoline or the a1 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. |
