mr-2266 has been researched along with Pain* in 9 studies
1 review(s) available for mr-2266 and Pain
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Functional response of multiple opioid systems to chronic arthritic pain in the rat.
Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis; Arthritis, Experimental; Benzomorphans; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Morphine; Naloxone; Nociceptors; Pain; Pituitary Gland, Anterior; Protein Precursors; Pyrrolidines; Rats; Receptors, Opioid; Sensory Thresholds; Spinal Cord; Thalamus | 1986 |
8 other study(ies) available for mr-2266 and Pain
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Interaction of pentazocine with calcium channel blocking drugs during chemical and thermal pain in mice.
The present study was designed to investigate the antinociceptive interaction of a clinically used opioid, pentazocine which produces its analgesic effect mainly through kappa receptors, with some calcium channel blockers (CCBs, viz. Diltiazem, flunarizine, nimodipine and verapamil--each representing one chemical class) in formalin and tail flick tests in mice. All the CCBs, except verapamil, significantly inhibited the formalin-induced pain response in a dose-dependent manner. However, none of these drugs affected tail flick latency at any of the studied doses. Pentazocine showed a significant antinociceptive response in both pain models, although a high dose was required to increase the tail flick latency. Pretreatment with all CCBs, individually enhanced the analgesic effect of pentazocine in both formalin and tail flick tests. In the latter test of nociception, a per se ineffective dose of pentazocine, showed a significant analgesic response in presence of CCB dose which itself was not effective in the test. Chronic concomitant administration of diltiazem with pentazocine did not prevent the development of tolerance to the opioid compound. However, diltiazem when given in combination with pentazocine to pentazocine-tolerant animals, it effectively reversed the tolerance. Results of the study thus suggest that concomitant treatment with CCBs, irrespective of their chemical nature, not only potentiate the antinociceptive effect of pentazocine in opioid naive animals in both tonic and acute nociceptive tests but also reverse the pentazocine tolerance. Topics: Analgesics, Opioid; Animals; Benzomorphans; Calcium Channel Blockers; Drug Interactions; Drug Tolerance; Female; Formaldehyde; Male; Mice; Pain; Pentazocine | 2000 |
Differential effects of specific delta and kappa opioid receptor antagonists on the bidirectional dose-dependent effect of systemic naloxone in arthritic rats, an experimental model of persistent pain.
In an attempt to determine the opioid receptor class(es) which underly the two opposing effects of naloxone in models of persistent pain, we tested the action of the selective delta antagonist naltrindole, and that of the kappa antagonist MR-2266 on the bidirectional effect of systemic naloxone in arthritic rats. As a nociceptive test, we used the measure of the vocalization thresholds to paw pressure. The antagonists were administered at a dose (1 mg/kg i.v. naltrindole, 0.2 mg/kg i.v. MR-2266), without action per se but which prevents the analgesic effect of the delta agonist DTLET (3 mg/kg, i.v.) or the kappa agonist U-69,593 (1.5 mg/kg, i.v.) respectively, and does not influence the effect of morphine (1 mg/kg i.v.) or the mu agonist DAMGO (2 mg/kg, i.v.) in these animals. In arthritic rats injected with the delta antagonist, the paradoxical antinociceptive effect produced by 3 micrograms/kg i.v. naloxone was not significantly modified (maximal vocalization thresholds (% of control) were 146 +/- 9% versus 161 +/- 7% in the control group). By contrast, the hyperalgesic effect produced by 1 mg/kg i.v. naloxone was significantly reduced (maximal vocalization thresholds were 87 +/- 4% versus 69 +/- 5% in the control group). In rats injected with the kappa antagonist, the antinociceptive effect of the low dose of naloxone was almost abolished (mean vocalization thresholds were 115 +/- 3% versus 169 +/- 7%) whereas the hyperalgesic effect of naloxone 1 mg/kg i.v. was not significantly modified (mean vocalization thresholds = 70 +/- 3% and 65 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Analysis of Variance; Animals; Arthritis; Benzomorphans; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Pain; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Vocalization, Animal | 1993 |
Involvement of corticotropin-releasing factor in the antinociception produced by interleukin-1 in mice.
Recombinant human interleukin-1 alpha (rHu-IL-1 alpha) has been indicated to produce central antinociception in the mouse phenylquinone writhing test, the antinociception being unaffected by naloxone. Because interleukin-1 has been demonstrated to be a potent releaser of corticotropin-releasing factor (CRF) from the hypothalamus, we were interested to see whether CRF is involved in the antinociception induced by rHu-IL-1 alpha. In the present study, we examined this question using the mouse phenylquinone writhing test, in which mice were injected with various doses of CRF and/or alpha-helical CRF-(9-41), a CRF antagonist. CRF inhibited writhing responses after i.v. and intracisternal (i.c.) administration. The antinociception elicited by i.v. administered CRF was antagonized by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). The antinociception elicited by i.e. administered CRF was antagonized by i.c. injection of alpha-helical CRF-(9-41) and s.c. treatment of opioid antagonists. rHu-IL-1 alpha-induced antinociception was attenuated by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). These findings suggest that CRF possesses antinociceptive efficacy by both peripheral and central mechanisms, and that the antinociception induced by rHu-IL-1 alpha is mediated, at least in part, by the peripheral action of CRF. Topics: Animals; Benzomorphans; Corticotropin-Releasing Hormone; Drug Interactions; Humans; Hypothalamus; Injections, Intravenous; Interleukin-1; Mice; Naloxone; Pain; Pain Measurement; Peptide Fragments; Recombinant Proteins | 1993 |
Selective opioid receptor agonists modulate mechanical allodynia in an animal model of neuropathic pain.
This study evaluated the antinociceptive effects of systemically administered selective opioid agonists of mu (DAMGO), delta (BUBU) and kappa (U 69593) receptors on the vocalization threshold to paw pressure in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. DAMGO (0.5-2 mg/kg), BUBU (1.5-6 mg/kg) and U 69593 (0.75-3 mg/kg) injected intravenously (i.v.) produced a potent long-lasting antinociceptive effect on both hind paws. The effects on the lesioned paw were clearly and statistically more potent than for the non-lesioned paw. The selective antinociceptive effect of 2 mg/kg DAMGO, 3 mg/kg BUBU and 1.5 mg/kg U 69593 were completely prevented by prior administration of the appropriate antagonists: 0.1 mg/kg naloxone, 1 mg/kg naltrindole and 0.4 mg/kg MR 2266. The present data clearly show that an acute i.v. injection of these selective opioid agonists induces potent antinociceptive effects in a rat model of peripheral neuropathy. These data are discussed with regard to the classical view that there is opioid resistance in neuropathic pain. Topics: Analgesics; Animals; Benzeneacetamides; Benzomorphans; Disease Models, Animal; Drug Interactions; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Male; Naloxone; Naltrexone; Narcotic Antagonists; Oligopeptides; Pain; Pain Measurement; Pain Threshold; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Vocalization, Animal | 1993 |
Inability of an opioid antagonist lacking negative intrinsic activity to induce opioid receptor up-regulation in vivo.
1. It has recently been suggested that opioid antagonists may be divided into those possessing negative intrinsic activity (e.g. naloxone) and those with neutral intrinsic activity (e.g. MR2266). 2. MR2266 was chronically administered to rats by subcutaneous infusion at a dose of 0.3 mg kg-1 h-1 for 1 week. 3. This dose reduced ingestive behaviour and blocked the antinociceptive effects of a kappa-agonist, indicating occupation of opioid receptors in vivo. 4. No supersensitivity could be detected to the antinociceptive actions of mu or kappa agonists, either one or two days after cessation of treatment. 5. No up-regulation of mu, delta or kappa binding sites was observed. 6. Since naloxone induces both supersensitivity and receptor up-regulation under equivalent conditions, the results suggest that negative intrinsic activity may be required for these phenomena to occur. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Benzomorphans; Binding, Competitive; Drinking; Eating; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Narcotic Antagonists; Pain; Pain Measurement; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Sensory Thresholds; Up-Regulation | 1991 |
Effects of the benzomorphan kappa-opiate, MR 2266 and its (+) enantiomer MR 2267, on thermonociceptive reactions in different strains of mice.
The effects of the benzomorphan kappa opiate MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in Swiss Webster, C57BL/6, BALB/c and DBA/2 strains of mice. In the hot plate (60 +/- 0.5 degrees C, cut-off time 120 s and tail immersion tests, MR 2266 (10 mg/kg, s.c., 15 min before) decreased, while MR 2267 (10 mg/kg s.c., 15 min before) increased the reaction latencies. In the hot plate test, the sensitivities for the effects of MR 2266 and MR 2267 on jump latency in different strains of mice were as follows: MR 2266; BALB greater than Swiss greater than C57BL greater than DBA and MR 2267; DBA greater than BALB = Swiss greater than C57BL. In the immersion test, for the hyperalgesic response of MR 2266, the rank order of strains was; BALB greater than C57BL and DBA greater than or equal to Swiss while the rank order for the analgesic effect of MR 2267 was; Swiss greater than DBA and BALB. The results indicate the presence of tonic kappa-receptor-mediated regulation of the spinal and supra-spinal thermonociceptive reactions which is stereospecific and strain dependent. Topics: Animals; Benzomorphans; Hot Temperature; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Narcotic Antagonists; Pain; Receptors, Opioid; Receptors, Opioid, kappa; Species Specificity; Stereoisomerism | 1990 |
Long-term blockade of mu-opioid receptors suggests a role in control of ingestive behaviour, body weight and core temperature in the rat.
Chronic subcutaneous infusion with a low dose (0.5 mg/kg/h) of naloxone via minipumps blocked the antinociceptive action of the mu-agonist, morphine, without affecting that of the kappa-agonist, U50488H. This dose resulted in a transient suppression in the rate of body weight gain and a sustained reduction in daily food intake (FI) and water intake (WI): this decrease was seen in both the light and dark phases. Naloxone also resulted in a reduction in resting core temperature (TC) in the light but not the dark phase. It did not affect the weight loss or hypothermia which accompanied 24 h food and water deprivation. Naloxone did, however, suppress FI and WI following deprivation and inhibited the recovery of body weight thereafter. The influence of naloxone upon FI, WI, TC and body weight was dose-dependent over 0.05-0.50 mg/kg/h. Increasing the dose to 3.0 mg/kg/h eliminated the antinociceptive action of U50,488H revealing a blockade of kappa- (in addition to mu-) receptors. This higher dose was not more effective in reducing FI, WI, body weight and TC than 0.5 mg/kg/h. Further, treatment with MR 2266, an antagonist (or weak partial agonist) with a higher activity at kappa-receptors than naloxone, was not more effective than naloxone in reducing FI, WI and body weight: further, it did not affect TC. Moreover, chronic infusion of bremazocine, (a kappa-agonist and mu-antagonist) reduced WI, FI, body weight and TC by a magnitude comparable to that of naloxone. Finally, chronic infusion of the mu-agonist, sufentanyl, led to a sustained rise in TC. It is concluded, that: (1) mu-opioid receptors may play a major role in the modulation of daily FI and WI and of body weight in freely behaving rats: this action is expressed in both the light and dark phases of the cycle and maintained following deprivation. The data provide no evidence for (but do not exclude) a particular role of kappa-receptors. (2) mu-Receptors play a physiological role in the modulation of TC in the light but not the dark phase of the daily cycle. Topics: Animals; Benzomorphans; Body Temperature Regulation; Body Weight; Circadian Rhythm; Drinking Behavior; Feeding Behavior; Fentanyl; Male; Naloxone; Pain; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, mu; Sufentanil | 1988 |
Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat.
Inoculation of the right hind paw with Mycobacterium butyricum rapidly led to swelling and inflammation. The afflicted limb showed an enhanced sensitivity to noxious pressure (hyperalgesia) and a reduced sensitivity to noxious heat 24 h following treatment. Both naloxone and MR 2266 (which has greater activity at kappa-opioid receptors) further increased the sensitivity to pressure (that is, potentiated the hyperalgesia) but did not affect the response to heat. They did not affect the response of the uninflamed paw. At 1 week, only MR 2266 was effective. At both 24 h and 1 week, the inflamed paw showed pronounced supersensitivity to the antinociceptive action of morphine against noxious pressure. At both 24 h and (to a greater extent) 1 week, a rise in levels of immunoreactive (ir)-dynorphin (DYN) was seen in the ipsilateral dorsal horn of the lumbar spinal cord. There was no alteration in the contralateral dorsal horn or in either ventral horn. Furthermore, levels of ir-met-enkephalin (ME) and ir-leu-enkephalin (LE) were unaffected. There was no difference in the density of mu-, delta- or kappa-binding sites in any part of the lumbar cord, at either 24 h or 1 week, between ipsilateral and contralateral tissue. By 3 and 5 weeks postinoculation, the symptoms had spread to the contralateral hind limb and ir-DYN was elevated in the contralateral dorsal horn and the ipsilateral ventral horn. At 5 weeks, levels of ir-ME and ir-LE also were increased in the ipsilateral and contralateral dorsal horns, but not in the contralateral ventral horn. Furthermore, levels of ir-DYN were increased in the cervico-thoracic spinal cord, and rats displayed adrenal hypertrophy and a rise in plasma levels of ir-beta-endorphin (beta-EP). These data indicate: (1) Peripheral inflammation localized to a single limb selectively modifies levels of ir-DYN in ipsilateral dorsal horn. The effect is specific to DYN as compared to ME and LE. The density of mu-, delta-, or kappa-receptors in the lumbar spinal cord is unmodified. (2) The altered response to opioid agonists and antagonists shown by rats with an inflamed limb may be selective to the injured tissue. (3) Alterations in opioid systems associated with unilateral hind limb inflammation may not be exclusively chronic in nature: they appear very rapidly (within 24 h) of the induction of pain. With time, the contralateral limb becomes affected and, eventually, the effects resemble those seen with generalized polyarthritis. Topics: Animals; Benzomorphans; Disease Models, Animal; Dynorphins; Endorphins; Hindlimb; Inflammation; Male; Naloxone; Pain; Rats; Rats, Inbred Strains; Receptors, Opioid; Spinal Cord | 1988 |