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 antagonistic effect of pseudoginoside-F11 (PF(11)) on the various actions of morphine was studied in mice. The results demonstrated that PF(11), at the doses of 4 and 8 mg/kg, PO, significantly inhibited morphine (10 mg/kg, SC)-induced memory impairment in the Morris water maze test. PF(11), at 4 mg/kg, PO, did not influence conditioned place preference per se, yet markedly blocked the conditioned place preference to morphine. PF(11), at the doses of 4 and 8 mg/kg, PO, also significantly antagonized morphine (5 mg/kg, SC)-induced analgesia tested by tail pinch method. PF(11), at 4 mg/kg, PO, did not influence locomotor activity per se, yet inhibited the development of the reverse tolerance, as shown by the increase in locomotor activity, to morphine. At the doses of 4 and 8 mg/kg, PO, PF(11) significantly antagonized the development of analgesia tolerance to morphine in the tail pinch test. Thus, the above results demonstrate for the first time that PF(11) can antagonize some actions of morphine. However, the mechanism of action of PF(11) merits further evaluation.
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PMID:Antagonistic effect of pseudoginsenoside-F11 on the behavioral actions of morphine in mice. 1089 76

Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na(+) channels are critical for experiencing pain sensation. We tested the hypothesis that menthol may block voltage-gated Na(+) channels in dorsal root ganglion (DRG) neurons. By use of a patch clamp, we evaluated the effects of menthol application on tetrodotoxin (TTX)-resistant Nav1.8 and Nav1.9 channel subtypes in DRG neurons, and on TTX-sensitive Na(+) channels in immortalized DRG neuron-derived F11 cells. The results indicate that menthol inhibits Na(+) channels in a concentration-, voltage-, and frequency-dependent manner. Menthol promoted fast and slow inactivation states, causing use-dependent depression of Na(+) channel activity. In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.
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PMID:Menthol pain relief through cumulative inactivation of voltage-gated sodium channels. 2217 48

Modulation of the transient receptor potential melastatin type-8 (TRPM8), the receptor for menthol acting as the major sensor for peripheral innocuous cool temperatures, has several important applications in pharmaceutical, food and cosmetic industries. In the present study, we designed 12 isoxazole derivatives and tested their pharmacological properties both in F11 sensory neurons in vitro, and in an in vivo model of cold allodynia. In F11 sensory neurons, single-cell Ca(2+)-imaging experiments revealed that, when compared to menthol, some newly-synthesized compounds were up to 200-fold more potent, though none of them showed an increased efficacy. Some isoxazole derivatives potentiated allodynic responses elicited by acetone when administered to rats subjected to sciatic nerve ligation; when compared to menthol, these compounds were efficacious at earlier (0-2 min) but not later (7-9 or 14-16 min) time points. Docking experiments performed in a human TRPM8 receptor model revealed that newly-synthesized compounds might adopt two possible conformations, thereby allowing to distinguish "menthol-like" compounds (characterized by high efficacy/low potency), and "icillin-like" compounds (with high potency/low efficacy). Collectively, these data provide rationale structure-activity relationships for isoxazole derivatives acting as TRPM8 agonists, and suggest their potential usefulness for cold-evoked analgesia.
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PMID:Isoxazole derivatives as potent transient receptor potential melastatin type 8 (TRPM8) agonists. 2409 58