Nd anhedonia, each of which are reasonably frequent comorbidities of epilepsy.
Nd anhedonia, both of that are reasonably common comorbidities of epilepsy. An assessment of XEN1101 in acute rodent models of depression and anhedonia was undertaken. The forced swim test (FST) is usually a model of behavioral despair, and is sensitive to several classes of antidepressant drugs. Mice received a single dose of 1 mg/kg or 3 mg/kg XEN1101, 30 mg/kg imipramine, or vehicle. Thirty minutes post-dose, animals have been placed into glass cylinders filled with water. Just after a period of vigorous activity, mice quit swimming and adopt an immobile posture. More than a 6-min test session, the 1 mg/kg and 3 mg/kg XEN1101 dose groups showed a dose-dependent trend towards elevated latency to immobility too as a dose-dependent reduction in time spent immobile (154 49.9 s and 142 42.8 s for 1 and three mg/ kg doses, respectively, compared to 201 42.9 s for car (p 0.05)); each indicative of an anti-depressant effect. The progressive ratio test (PRT) is usually a model of anhedonia. The impact of XEN1101 around the motivation of trained rats to respond with a lever press to get a food reward was assessed. The rats followed a progressive schedule of reinforcement in which the number of lever presses necessary to acquire a meals reward enhanced for successive reinforcers. The break point was defined MAO-B list because the point at which a rat failed to earn a food pellet in 20 min. The number of meals pellets earned was the primary measure of efficacy, with increases indicating improvements in anhedonia. Within a crossover design, rats received a single dose of 1, three, or 8 mg/kg XEN1101, 0.6 mg/kg amphetamine (as a optimistic handle), or car. XEN1101 significantly increased the number of food pellets earned at the break point for each the three mg/kg (n = 12.five 0.four) and 8 mg/kg doses (n = 12.eight 0.5), respectively, compared to n = 11.5 0.5 for car (p 0.05 and p 0.01, respectively). The results from these two research assistance a potential benefit of XEN1101 in mood problems.ASENT2021 Annual Meeting AbstractsAbstract 21 Anticonvulsant Effects from the Differentiated Kv7 Channel Potentiator XEN1101 in Combination with Typically Utilised Anti-seizure Drugs J.P. Johnson, Jr., Girish Bankar, Celine Dube, Parisa Tari, Karen Nelkenbrecher, Matthew Waldbrook, Nina Weishaupt, Gregory Beatch, Jeff Bechard, Rostam Namdari, Robin Sherrington, Alison Cutts, Charles Cohen, James Empfield; Xenon Pharmaceuticals, Inc. XEN1101 is really a positive allosteric modulator of Kv7 Urotensin Receptor supplier channels getting created for the treatment of epilepsy. Mixture of anti-seizure drugs (ASDs) is popular in clinical practice. Hence we examined the prospective for combination therapy with XEN1101 and also other ASDs. The efficacy of XEN1101 was evaluated in mixture with valproic acid, phenytoin, or levetiracetam within the direct current maximum electroshock seizure assay (DC-MES). The combined efficacy of XEN1101 and levetiracetam was also evaluated in the 6-Hz psychomotor seizure assay (6 Hz). We tested the efficacy of XEN1101 in combination with phenytoin within the DC-MES assay. A weakly efficacious dose of phenytoin (two mg/kg protected 25 of mice) was combined with XEN1101 at 0.75, 1, 1.5, and two.five mg/kg inside the DC-MES assay. XEN1101 was helpful, with a total plasma EC50 of 0.154 when dosed alone and 0.04 when dosed in combination with phenytoin, a three.85-fold enhance in apparent potency. We subsequent tested XEN1101 in the DC-MES assay in combination with valproic acid. A weakly efficacious dose of XEN1101 (1 mg/kg protected 30 of mice) was combined w.
