No abstract

Agmatine, an amine and organic cation, is formed by the decarboxylation of L-arginine by arginine decarboxylase. It binds to alpha(2)-adrenergic and imidazoline receptors. It blocks N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and inhibits nitric oxide (NO) synthase. Because the importance of NMDA receptors and the NO system are well known in seizure activity, this study was designed to investigate the effect of agmatine on electrically and chemically induced seizures by using maximal electroshock (MES) and pentilentetrazole (PTZ) models in mice. Initial studies established convulsive current 50 (CC(50)) for MES and effective dose 50 (ED(50)) for PTZ to produce seizures. Agmatine (20, 40, 80, and 100 mg/kg intraperitoneally) increased the threshold of seizures in MES dose dependently. In PTZ-induced convulsions, the highest dose of agmatine (100 mg/kg) increased the seizure onset time and decreased percent survival. The percentage of grade V seizures was found to be increased by agmatine doses greater than 20 mg/kg.

Agmatine is a polycationic amine synthesized from L-arginine by arginine decarboxylase in brain and several tissues. It binds to N-methyl-D-aspartate (NMDA) subtype of glutamatergic, alpha(2)-adrenergic and imidazoline (I) receptors. The present study was designed to investigate effect of agmatine on acute and mononeuropathic pain after chronic constriction injury (CCI). CCI was created by four loose ligations around the right sciatic nerve. The analgesic threshold in rats was evaluated by using thermal hyperalgesia/allodynia (THA) at 4 degrees C. The evaluations were made preoperatively, on postoperative day 15, and after drug administration. Agmatine (10, 20, 40, 80, and 100 mg/kg) was administered intraperitoneally for 5 days beginning on postoperative day 15. Agmatine significantly reduced the hyperalgesia in all doses applied. When agmatine was injected intraperitoneally (10, 20, 40, 80, and 100 mg/kg), it increased the nociceptive threshold in the tail-immersion test in a dose-dependent manner, but it had no effect in the hot-plate test. This effect of agmatine in the tail-immersion test was blocked by both yohimbine (1 mg/kg) and idazoxan (0.5 mg/kg). When agmatine was administered intracerebroventricularly (25-200 microg/10 microL), it increased the nociceptive threshold in the hot-plate but not in the tail-immersion test. We conclude that agmatine, an endogenous substance derived from arginine, can modulate both acute and chronic pain.

The study investigated the activity of harmane on maximal electroshock seizures (MES) and seizures induced by pentilentetrazole (PTZ) in mice. Initial studies established convulsive current 50 (CC(50)) values or MES and effective dose 50 (ED(50)) for PTZ to produce seizures. Harmane (2.5, 5.0, or 10 mg/kg intraperitoneally) increased the threshold of seizures in MES dose-dependently. The convulsions produced by PTZ were decreased by the low dose of harmane (2.5 mg/kg), but the high dose of harmane (10 mg/kg) resulted in worse grade V convulsions followed by more lethality compared with PTZ alone. Therefore, harmane seems to be protective against grand mal seizures in the MES model but not against a petit mal seizure model (PTZ) in mice.

This study was designed to investigate the effect of the endogenous beta-carboline, harmane, on neuropathic pain produced by chronic constriction injury (CCI) of the sciatic nerve. Thermal allodynia evaluations were made preoperatively, postoperatively on the fifteenth day, and after harmane administration. Harmane (1, 2.5, 5, 10, or 20 mg/kg) was administered intraperitoneally for 5 days beginning from postoperative day 15. Treatment with harmane had a profound anti-allodynic effect in a dose-dependent manner. In conclusion, harmane might provide a new approach to treatment of neuropathic pain.