Antinociceptive activity of narcotic agonist and partial agonist analgesics and other agents in the tail-immersion test in mice and rats

331

139

1To investigate the opiate receptors that mediate antinociception, the activity profiles of opioid analgesic drugs have been determined against different nociceptive stimuli in the mouse and rat.2 In tests that employ heat as the nociceptive stimulus, p-opiate receptor agonists, such as morphine, pethidine and dextropropoxyphene, had steep and parallel dose-response curves and were capable of achieving maximum effects. In addition, the antinociceptive potency ratios of these drugs in heat tests were similar to those for analgesia in man. 3 The K-agonists, such as ethylketazocine, nalorphine, Mr2034 and pentazocine, were essentially inactive against heat nociception except at doses that caused sedation and motor incapacitation. 4 In the writhing and paw pressure tests both j-and a--agonists produced steep and parallel dose-response curves. 5 It is concluded that both t-and K-opiate receptors mediate antinociception in animals and that the interactions of analgesic drugs with these receptors may be classified in terms of their antinociceptive activities against qualitatively different nociceptive stimuli.

Section: Discussioncontrasting

confidence: 57%

A Classification of Opiate Receptors That Mediate Antinociception in Animals

Tyers

1980

331

139

“…Moreover, some commonly-used analgesic tests, especially those employing heat as the noxious stimulus, do not reliably detect analgesics of the opioid 'agonist-antagonist' (Martin, 1967) class. For example, drugs such as nalbuphine, buprenorphine and pentazocine are reported to have little effect on reaction time in response to thermal stimuli (O'Callaghan & Holtzman, 1975;Sewell & Spencer, 1976;Luttinger, 1985;Zimet et al, 1986). However, these drugs produce potent antinociceptive effects against a wide range of chemical stimuli in abdominal constriction models (Taber et al, 1964;Collier et al, 1968;Tyers, 1980).…”

Section: Introductionmentioning

confidence: 99%

Differential sensitivity of antinociceptive tests to opioid agonists and partial agonists

Shaw

Rourke

Burns

1988

1 The antinociceptive activity of a range of opioid agonists and agonist-antagonist analgesics was determined in mice by use of the 550C hot plate and abdominal constriction assays. 2 Opioid agonists were approximately 10 times more effective in the abdominal constriction assay. 3 The agonist-antagonists produced analgesia only in the abdominal constriction assay, and antagonized the antinociceptive action of opioid agonists in the 550C hot plate test. 4 These differences were shown to be attributable to the different levels of stimulus employed in the two tests. 5 By comparing the antagonist potencies of the agonist-antagonists in the 550C hot plate test with their antinociceptive ED50 values in the abdominal constriction assay, an index of intrinsic activity was calculated.

“…Anaesthesia duration was measured as the time from the loss of the recovery of the righting reflex by an animal. The tail-flick method was used as a measure of analgesia (Sewell & Spencer, 1976). The test was performed by immersing the animal's tail in hot water at 58°C and the time for removal of the tail was measured.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Opiate‐like Analgesic Activity in General Anaesthetics

Lawrence¹,

Livingston²

1981

1 The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro.2 Naloxone (10mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin.3 Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail-flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone. (IC50 = 40 nM). 6 On the stimulated guinea-pig ileum, Met-enkephalin and morphine inhibited the contractions, the IC50 values were 30 nm and 50 nm respectively. The anaesthetics ketamine (IC50 = 10 FM) and Althesin (IC50=8,UM) were active. Xylazine (IC50=12nM) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 p.M produced a 1000 fold shift in the opiate dose-response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone. 7 The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised.8 Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.