Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of alpha 1 receptors in antinociception was investigated in the formalin test, a well established test of tonic pain. The effect of systemic injections of selective alpha 1-adrenergic agonists (phenylephrine and methoxamine), a mixed alpha agonist selective for alpha 2 receptors (ST-91), and 2 adrenergic antagonists (prazosin and idazoxan) was measured in groups of Long-Evans rats. All agonists tested produced significant antinociception in this test. Dose-response curves for each agonist were statistically parallel and equally efficacious (100% antinociception). Prior injection of 0.15 mg/kg prazosin (an alpha 1 antagonist) completely antagonized the antinociception produced by either an ED50 or a maximally effective dose of each agonist tested. Idazoxan (0.5 mg/kg), an alpha 2 antagonist, was without effect on the antinociception produced by phenylephrine or methoxamine. ST-91 produced significant antinociception in the presence of idazoxan although the response was different from that obtained with ST-91 alone. The observed antinociception in the formalin test was not due to drug-induced changes in peripheral inflammation as measured using plethysmometry. Moreover, none of the drugs tested produced significant changes in coordinated motor behavior (accelerated rotarod test) at doses that produced significant analgesia (ED50). We conclude that alpha 1 receptors contribute significantly to adrenergic analgesia in the formalin test by an undefined action on sensory processing mechanisms.
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PMID:Systemic injections of alpha-1 adrenergic agonists produce antinociception in the formalin test. 135 19

Agmatine blocks morphine withdrawal symptoms and enhances morphine analgesia in rats. Yet, the role of agmatine in the pharmacological effects of other abused drugs has not been investigated. The present study investigates the effect of agmatine administration on the hypothermic response to cannabinoids. Hypothermia is an effective endpoint because cannabinoid agonists produce a rapid, reproducible, and significant decrease in body temperature that is abolished by cannabinoid CB(1) receptor antagonists. WIN 55212-2, a cannabinoid agonist, was administered to rats by itself and with agmatine. WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.) caused a significant hypothermia. Agmatine (10, 25 and 50 mg/kg, i.p.) was ineffective. For combined administration, agmatine (50 mg/kg, i.p.) enhanced the hypothermic effect of WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.). The enhancement was strongly synergistic, indicated by a 2.7-fold increase in the relative potency of WIN 55212-2. The central administration of agmatine (25 and 50 mug/rat, i.c.v.) significantly increased the hypothermic effect of WIN 55212-2 (2.5 mg/kg, i.m.). This indicates that agmatine acts through a central mechanism to augment cannabinoid-evoked hypothermia. Idazoxan (2 mg/kg, i.p.), an imidazoline antagonist, blocked the enhancement by agmatine, thus suggesting that imidazoline receptor activation is required for agmatine to enhance cannabinoid-evoked hypothermia. The present data reveal that agmatine and a cannabinoid agonist interact to produce a hypothermic synergy in rats. These results show that agmatine acts in the brain and via imidazoline receptors to enhance cannabinoid-evoked hypothermia.
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PMID:Agmatine and a cannabinoid agonist, WIN 55212-2, interact to produce a hypothermic synergy. 1710 46

Clonidine, an alpha2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia. This study examined the influence of sulfisoxazole (ETA receptor antagonist) on clonidine analgesia. Male Swiss Webster mice were used to determine antinociceptive response of drugs by measuring tail-flick latency. The effect of clonidine (0.3, 1.0, and 3.0 mg/kg, i.p.) alone or in combination with sulfisoxazole (25, 75, and 225 mg/kg, p.o.) on analgesia and body temperature was determined. Clonidine produced a dose-dependent analgesia and hypothermia. Sulfisoxazole (25, 75, and 225 mg/kg), when administered with clonidine (0.3 mg/kg), significantly potentiated (31% increase in area under the curve (AUC)) the analgesic effect of clonidine. Yohimbine (alpha2-adrenergic receptor antagonist) did not affect analgesic effect of clonidine plus sulfisoxazole. Idazoxan (I1-imidazoline and alpha2-adrenergic receptor antagonist) reduced (47% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. Treatment with naloxone reduced (46% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. The effect of another ETA receptor antagonist, BMS-182874 (2, 10, and 50 microg, i.c.v.) was studied, and it was found that the dose of 10 microg significantly potentiated (26% increase in AUC) the analgesic effect of clonidine. These results indicate that sulfisoxazole, an ETA receptor antagonist, potentiates the analgesic effect of clonidine, which could be mediated through I1-imidazoline receptors and opioid receptors.
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PMID:Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole. 2055 23