Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, fever, and inflammation. Among them are celecoxib and ketorolac, whose efficacy is dependent on the inhibition of COXs and seems to be modulated by additional mechanisms that would contribute to analgesic efficacy. On the other hand, the interaction of NSAIDs with other types of analgesics, especially opioids, is often poorly identified. The objective of this work was to evaluate the effect of the opioid antagonists: naltrexone, naltrindole, and norbinaltorphimine on the efficacy of celecoxib and ketorolac in murine models of tonic and visceral pain induced by chemical stimuli, such as contortions induced by acetic acid and the formalin hind paw test. The antinociceptive potency of celecoxib and ketorolac was assessed using a dose-response curve from 0.1-10 mg/kg, i.p. before and after pretreatment of mice with 1 mg/kg i.p. of the opioid antagonist’s naltrexone, naltrindole, or norbinaltorphimine. Celecoxib was 1.58 to 4.85 times more potent than ketorolac. The effect of both NSAIDs was unequally modified by opioid antagonists. Thus, the efficacy of ketorolac increased in the writhing test and in the phase I formalin trial, while that of celecoxib only increased in the phase II formalin trial. The results demonstrate that ketorolac and celecoxib induce significant antinociception, whose efficacy was increased by specific opioid receptor antagonists, suggesting that the antinociception induced by ketorolac and celecoxib is dependent on opioid receptors.

Opioids are among the most effective pain relievers available; however induced antinociception has not been extensively studied in different animal pain models. The studies have been conducted with isolated opioids only, but have not been used in combination, as multimodal analgesia. In the present study, the pharmacological interaction of morphine with fentanyl was evaluated in different murine pain models by means of isobolographic analysis. In control animals, morphine and fentanyl produced a dose-related antinociceptive action in the murine assays and comparing the rank of potency was formalin hind paw phase I > formalin phase II > tail flick. The coadministration of morphine with fentanyl, in a fixed relation 1:1 of their ED50, produces a synergistic interaction of different magnitude. The study shows that fentanyl is more effective than morphine. This disparity could be explained according to the suggestions that opioids could be acting through other targets either by different binding capacity, by the regulation or activation of non-opioid receptors. Furthermore, coadministration of morphine with fentanyl induces synergism in the murine trials, confirming the antinociceptive and anti-inflammatory capacity of the opioids.

Non-steroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of pain by their analgesic, anti-inflammatory, and antipyretic properties. NSAIDs act via inhibition of cyclooxygenase enzymes, COX-1, COX-2 and COX-3. In this study, the antinociceptive activity of the dextrorotatory enantiomers of S (+) configuration of ketoprofen, denominate, dexketoprofen (DEX), was evaluated, before and after the pretreatment of mice with N(ω)-nitro-L-arginine methyl ester (L-NAME), in two models of pain. In one model of tonic pain, the tail-flick (TF) assay, and in a second model of phasic pain, the acetic acid writhing test (WT). (DEX) administration produced a dose-dependent antinociceptive effect in both murine assays, but with different potency. The dose that produced 50 % of the maximum possible effect (ED50) of antinociception of the WT was 3.87-fold more potent than TF. The pretreatment of mice with 1, 3, or 10 mg/kg, i.p of L-NAME produced a significant decrease of the antinociceptive effect of DEX, reflected with an important increase of ED50 in both assays. In conclusion, the results the application of DEX produced antinociception in the WT and TF models, and in this effect, the activation of the NO pathway plays an important role.

Amlodipine besylate is a long-acting calcium channel blocker which has proved to be very potent in the curation of elevated blood pressure. It is a relatively new antihypertensive drug which is commonly prescribed as a single oral dose. Eleven (11) male wistar rats of 250g average body weight were used to determine the effect of Amlodipine besylate on the male reproductive hormones. Three dose levels (0.5, 1.0 and 10mg/kg) were used. The rats were all sacrificed on the eight day following treatment and the serum collected was sent for hormonal assay. The results obtained showed normal values of the reproductive hormones when compared with the control. This study strongly suggests that there was no significant reduction in the values of the reproductive hormones even at the highest dose administered. It could be said that Amlodipine besylate is good for the treatment of hypertension.