Mechanisms involved in the antinociception caused by agmatine in mice

作者：Santos ARS^*; Gadotti VM; Oliveira GL; Tibola D; Paszcuk AF; Neto A; Spindola HM; Souza MM; Rodrigues ALS; Calixto JB

来源：Neuropharmacology, 2005, 48(7): 1021-1034.

DOI：10.1016/j.neuropharm.2005.01.012

• agmatine
• antinociception
• imidazoline receptors
• alpha(2)-adrenergic receptors
• nitric oxide systern
• 5-HT receptors

The present study examined the antinociceptive effects of agmatine in chemical behavioural models of pain. Agmatine (1-30 mg/ kg), given by i.p. route, 30 min earlier, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 5.6 mg/kg. Given orally, 60 min earlier, aginatine (10-300 mg/kg) also produced dose-related inhibition of the visceral pain caused by acetic acid, with mean ID50 value of 147.3 mg/kg. Agmatine (3-100 mg/kg, i.p.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 43.7 Lind 19.5 mg/kg, respectively. Moreover, agmatine (1-100 mg/kg, i.p.) caused marked inhibition of both phases of formalin-induced pain, with mean ID50 values for the neurogenic and the inflammatory phases of 13.7 and 5.6 mg/kg, respectively. The antinociception caused by agmatine in the acetic acid test was significantly attenuated by i.p. treatment of mice With L-arginine (precursor of nitric oxide, 600 mg/kg), naloxone (opioid receptor antagonist, 1 mg/kg), p-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days), ketanserin (a 5-HT2A receptor antagonist, 0.3 mg/kg), ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg), yohimbine (an alpha(2)-adrenoceptor antagonist, 0.15 mg/kg) or by efaroxan (an I-1 imidazoline/alpha(2)-adrenoceptor antagonist, I mg/kg). In contrast, agmatine antinociception was not affected by i.p. treatment of animals with pindolol (a 5-HT1A/1B receptor antagonist, I mg/kg) or idazoxan (an 12 imidazoline/a2-adrenoceptor antagonist, 3 ing/kg). Likewise, the antinociception caused by agmatine was not affected by neonatal pre-treatment with capsaicin. Together, these results indicate that agmatine produces dose-related antinociception in several models of chemical pain through mechanisms that involve an interaction with opioid, scrotonergic (i.e., through 5-HT2A and 5-HT3 receptors) and nitrergic systems, as well as via an interaction with alpha(2)-adrenoceptors and imidazoline l(1) receptors.

• 出版日期2005-6