Involvement of the nitric oxide/cyclic guanylate monophosphate pathway in the pilocarpine-induced seizure model in mice.

The present study was designed to investigate the involvement of the nitric oxide (NO)/cyclic guanylate monophosphate pathway in pilocarpine-induced seizures in mice. Male Swiss mice (26-32 g) were used as the in vivo model. The following pharmacological tools were utilized: the non-selective NO synthase (NOS) inhibitor L-NAME (10 mg/kg, i.p.), a preferential inducible NOS (iNOS) inhibitor aminoguanidine (25 mg/kg, i.p.), a highly specific iNOS inhibitor 1400W (2.5 mg/kg, i.p.), the NO donor L-arginine (150 mg/kg, i.p.), and the soluble guanylyl cyclase inhibitor ODQ (10 mg/kg, i.p.). The animals were divided into groups (n = 8) and pretreated for 30 min before receiving pilocarpine (400 mg/kg, i.p.), while the control group received only pilocarpine. They were observed for 60 min to measure initial seizure latency, latency till death, and mortality. An administration of L-NAME or ODQ delayed the onset of initial seizure, increased latency till death, and produced a 25% survival rate. Aminoguanidine increased the initial seizure and latency until death, and administration of 1400W did not have an effect. Incremental increases of NO by L-arginine were capable of decreasing the seizure and death latency. These results support the idea that the constitutive NOS, probably neuronal NOS, followed by soluble guanylyl cyclase activation is involved in the convulsive responses caused by pilocarpine administration.

Antinociceptive activity of carvacrol (5-isopropyl-2-methylphenol) in mice.

OBJECTIVES: Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol which is present in the essential oil of oregano and thyme. We have investigated the behavioural effects of carvacrol in animal models of pain, such as acetic acid-induced abdominal constriction, formalin and hot-plate tests in mice. The spontaneous motor activity of animals treated with carvacrol was investigated using open-field and rotarod tests. METHODS: Carvacrol was administered orally, at single doses of 50 and 100 mg/kg while indometacin (5 mg/kg), morphine (7.5 mg/kg) and diazepam (2 mg/kg) were used as standard drugs. Naloxone (1 mg/kg) and l-arginine (150 mg/kg) were used to elucidate the possible antinociceptive mechanism of carvacrol on acetic acid-induced abdominal constriction and formalin tests. KEY FINDINGS: The results showed that carvacrol produced significant inhibitions on nociception in the acetic acid-induced abdominal constriction, formalin and hot-plate tests. In the open-field and rotarod tests carvacrol did not significantly impair the motor performance. The effect of the highest dose of carvacrol in mice in the acetic acid-induced abdominal constriction and formalin tests were not reversed by naloxone or l-arginine. CONCLUSIONS: Based on these results, it has been suggested that carvacrol presents antinociceptive activity that may not act through the opioid system nor through inhibition of the nitric oxide pathway.