Intrathecal co-administration of morphine and nimodipine produces higher antinociceptive effect by synergistic interaction as evident by injecting different doses of each drug in rats
| Autor: | Subrata Basu Ray, Shashi Wadhwa, Deep Narayan Srivastava, Dilip Verma, Himanshu Gupta, R. K. Ahuja |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Tail Side effect Narcotic Antagonists medicine.medical_treatment Receptors Opioid mu Pain (+)-Naloxone Motor Activity Pharmacology Animals Medicine Rats Wistar Nimodipine Saline Injections Spinal Pain Measurement Dose-Response Relationship Drug Morphine Naloxone business.industry Drug Administration Routes Drug Synergism Long-term potentiation Calcium Channel Blockers Rats Analgesics Opioid Disease Models Animal Nociception Systemic administration business medicine.drug |
| Zdroj: | European Journal of Pharmacology. 561:46-53 |
| ISSN: | 0014-2999 |
| Popis: | Earlier, we reported that morphine-nimodipine combination produces significantly higher antinociception after intrathecal but not after systemic administration in mice. Different doses of morphine and nimodipine (5 microg of morphine, 5 microg of nimodipine, 5 microg each of morphine and nimodipine, 10 microg of morphine, 10 microg of nimodipine, 10 microg morphine with 5 microg nimodipine and 5 microg of morphine with 10 microg of nimodipine) were now injected intrathecally in Wistar rats to further characterise this antinociceptive effect. The acute antinociceptive effect was measured by the tail-flick test between 15 min to 7 h. The onset of maximum antinociception (100% MPE) was earlier (by 15 min) in nimodipine (5 microg) than in morphine (5 microg) treated group (by 30 min). Though earlier in onset, 5 microg nimodipine produced transient antinociception, which was significantly higher than saline treated controls for the initial 30 min only. Morphine (5 microg) produced significantly higher antinociception between 15 min to 3:30 h in comparison to control animals. However, co-administration of both morphine and nimodipine led to significantly higher antinociception than morphine alone at 4:00 h and also between 5:00 to 6:30 h. Interestingly, the combined antinociceptive action of morphine and nimodipine was not significantly different from 10 microg of morphine, which indicated synergistic interaction. Naloxone (5 mg/kg) could reverse this antinociceptive effect of morphine-nimodipine combination though it failed to reverse nimodipine (5 microg)-mediated antinociception at 15 min. Increasing the dose of either morphine or nimodipine to 10 mug did not increase antinociception except between 6:30-7:00 h. No obvious side effect was noted after administration of either morphine or nimodipine or both. |
| Databáze: | OpenAIRE |
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