Studies on the antinociceptive action of α‐agonist drugs and their interactions with opioid mechanisms

Abstract

1A modified abdominal constriction test, whereby the drugs used are injected intraperitoneally when the writhing response is maximal, has been used to study the antinociceptive activity of various sympathomimetic drugs. Of those tested, clonidine was the most potent, with an ID50 value in the nanomolar range. (-)-Isoprenaline, (-)-adrenaline and (-)-noradrenaline were only a little less potent. Phenylephrine, the least potent, had only about one-sixtieth of the activity of clonidine. 2 The antinociceptive action appears to occur within the peritoneum, since it was apparent almost immediately after the drugs were injected and was produced by doses far smaller than were effective by the subcutaneous route. 3 ac-Adrenoceptors appear to be involved in the reaction, since noradrenaline showed stereospecificity, and the a-adrenoceptor antagonists phentolamine and piperoxan both shifted the dose-response curves of the a-adrenoceptor agonist drugs to the right, usually parallel to the control curves.4 The high antinociceptive potency of clonidine and oxymetazoline, indicate the importance of a2-adrenoceptors and this was supported by the finding that piperoxan was a more effective antagonist than phentolamine. The moderate potency of phenylephrine suggests that aoadrenoceptors may also be involved, although the selective al-antagonist, prazosin, did not antagonize noradrenaline and had antinociceptive activity of its own. 5 P-Adrenoceptors also appear to be involved in the antinociceptive response, since propranalol antagonized the effect of isoprenaline, but not that of clonidine. 6 Piperoxan was a very effective antagonist of morphine, while phentolamine had a weaker action. Naloxone had little action against the a-adrenoceptor agonists. 7 Mice pretreated with clonidine or oxymetazoline but not noradrenaline showed a very great cross-tolerance to morphine. Morphine pretreatment caused marked desensitization of itself, but little cross-tolerance to clonidine or oxymetazoline.8 It is suggested that sensory nerves in the mouse peritoneum have a2-and P-adrenoceptors on their terminals, and possibly al-receptors also. It is possible that when activated by the appropriate agonists they depress the generation of pain impulses. There is an interaction between the a-adrenoceptors and opioid receptors in the mouse peritoneum.

Anti–inflammatory and analgesic activities of Melanthera scandens

“…Acetic acid causes inflammatory pain by inducing capillary permeability and in part through local peritoneal receptors from peritoneal fluid concentration of PGE 2 and PGF 2毩 [24] . This test alone can not specify the involvement of either central or peripheral activity [25] .…”

“…Carrageenin-induced mice hind paw oedema Increase in the mice hind paw linear circumference induced by plantar injection of the phlogistic agent was used as the measure of acute inflammation [11] . Adult albino mice of either sex were used after 24 h fast and deprived of water only during experiment. Inflammation of the hind paw was induced by injection of 0.1 mL of freshly prepared carrageenin suspension in normal saline into the sub plantar surface of the hind paw.…”

“…The leaf extract (37, 74 and 111 mg/kg i.p.) and ASA (100 mg/kg orally) were administered to 24 h fasted mice 1 h before the induction of inflammation. Control group received 10 mL/kg of distilled water orally.…”

“…The first of the nociceptive response normally peaks 5 min after injection and the second phase 15-30 min after formalin injection, representing the neurogenic and inflammatory pain responses, respectively [15] . Adult albino mice (23)(24)(25)(26)(27) g) of either sex randomized into five groups of 6 mice each were used for the experiment. The mice were fasted for 24 h before being used but allowed access to water.…”

“…The animals in group 1 (negative control) received 10 mL/kg of normal saline, groups 2-4 received 37, 74 and 111 mg/kg doses of the extract, while group 5 received 100 mg/kg of acetylsalicylic acid 30 min before being challenged with buffered formalin. The responses were measured for 5 min after formalin injection (first phase) and [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] min after formalin injection (second phase).…”