Abstract Title:

Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice.

Abstract Source:

Behav Brain Res. 2016 Mar 22. Epub 2016 Mar 22. PMID: 27016427

Abstract Author(s):

Paula Mosińska, Katarzyna Socała, Dorota Nieoczym, Moshe Laudon, Martin Storr, Jakub Fichna, Piotr Wlaź

Article Affiliation:

Paula Mosińska

Abstract:

The anticonvulsant activity of melatonin (MLT) have been tested in several in vivo models and against different convulsive stimuli. Although MLT exerts high affinity towards melatonin receptors (MTs), the potential usefulness in the treatment of epilepsy is limited mainly due to its short half-life. Therefore, the purpose of the present study was to compare the anticonvulsant properties of novel MT agonists Neu-P11 and Neu-P67 with MLT in mice. The anticonvulsant activity of tested compounds was evaluated in pentylenetetrazole-(PTZ) and electrically-induced convulsions. The effect of studied compounds on motor coordination and skeletal muscular strength in mice was assessed in the chimney test and grip test, respectively. The locomotor activity after administration of the tested compounds was also evaluated. In the MEST and 6-Hz tests, only MLT (50 and 100mg/kg, i.p.) significantly increased the seizure threshold. The i.p. administration of MLT (100mg/kg) and Neu-P67 (200mg/kg) resulted in a significantly elevated PTZ seizure threshold for forelimbs tonus. The compounds did not affect muscle strength. No alterations in motor coordination were noted. However, the locomotor activity was significantly decreased after administration of all tested compounds. Our study confirms the anticonvulsant potency of MLT and shows that novel synthetic MT agonists Neu-P11 and Neu-P67 have no effect on epileptic seizures in mice. Our data suggest that the activation of MT can be used in the treatment of seizures, but further pharmacological characterization is needed to understand the anticonvulsant activity of MLT and to design efficient MT-targeting antiepileptic drugs.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Anticonvulsants : CK(678) : AC(253)

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