The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha 2-adrenoceptors.
Recent demonstrations of the anticonvulsant properties of agmatine suggest it may be considered as a potential adjunct for protection against seizure. We investigated the possibility of an additive anticonvulsant effect between low doses of agmatine and morphine. The thresholds for the clonic seizures induced by the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist, pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1-3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threshold. Pretreatment with a per se non-effective dose of agmatine (1mg/kg) potentiated the anticonvulsant effect of morphine. The combination of subeffective doses of agmatine and morphine led to potent anticonvulsant effects. The pro-convulsant effect of morphine was attenuated by agmatine. Yohimbine with a dose (1mg/kg) incapable of affecting seizure threshold reversed the effect of agmatine on both anticonvulsant and pro-convulsant effects of morphine. These results suggest that agmatine potentiates the anticonvulsant effect of morphine and alpha 2-adrenoceptors may be involved in this effect.
Riazi
Kiarash
K
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Honar
Hooman
H
Homayoun
Houman
H
Rashidi
Narges
N
Kiani
Samira
S
Ebrahimkhani
Mohammad Reza
MR
Noorian
Ali Reza
AR
Ghaffari
Kamyar
K
Jannati
Ali
A
Dehpour
Ahmad Reza
AR
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use*; D010433:Pentylenetetrazole; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000376:Agmatine; D009020:Morphine; D010433:Pentylenetetrazole