title: The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice.
abstract: Melatonin, the major hormone produced by the pineal gland, has a number of functions in mammals, for example, its function as an anticonvulsant. Agmatine, a biogenic amine formed by decarboxylation of L-arginine by arginine decarboxylase, also has anticonvulsant effects. This study investigated the effect of the interaction of melatonin and agmatine on seizure susceptibility in the mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. Further, the researchers investigated the involvement of melatonin receptors in this interaction using luzindole, a ML(1/2) receptor antagonist and prazosin, a ML(3) receptor antagonist. Melatonin, at 40 and 80 mg/kg, and agmatine, at 10 and 20mg/kg, exerted anticonvulsant effects. Luzindole, at 1.25 and 2.5mg/kg, or prazosin, at 0.5mg/kg, did not change the seizure threshold as compared with that of vehicle-treated mice. The anticonvulsant effect of melatonin (40 and 80 mg/kg) was prevented by luzindole (2.5mg/kg) (P<0.001) but not prazosin (0.5mg/kg), indicating the possible involvement of ML(1/2) receptors in the anticonvulsant effect of melatonin. Agmatine (5mg/kg) significantly increased the anticonvulsant effect of both the noneffective dose (20mg/kg) (P<0.05) and the effective dose (80 mg/kg) (P<0.001) of melatonin. Luzindole (2.5mg/kg), but not prazosin (0.5mg/kg), decreased the anticonvulsant effect of agmatine (20mg/kg) (P<0.05). Luzindole (2.5mg/kg), but not prazosin (0.5mg/kg), also decreased the seizure threshold when agmatine (5mg/kg) was administered before melatonin (20mg/kg); the decrease was significant compared with that of the group that received only agmatine and melatonin (P<0.001). In conclusion, melatonin and agmatine exhibit an additive effect in decreasing pentylenetetrazole-induced seizure threshold in mice, probably through ML(1/2) receptors.
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Hojati
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000376:Agmatine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D011224:Prazosin / Q000627:therapeutic use; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D000376:Agmatine; D008550:Melatonin; D010433:Pentylenetetrazole; D011224:Prazosin