Dextromethorphan, 3-methoxymorphinan, and dextrorphan have local anaesthetic effect on sciatic nerve blockade in rats.

Dextromethorphan has been used as an antitussive for more than 40 years and is considered a drug with a good margin of safety. The aim of the study was to evaluate whether dextromethorphan and its metabolites--3-methoxymorphinan and dextrorphan--had local anaesthetic effects. Using a method of sciatic nerve blockade in rats, the potencies and durations of actions of dextromethorphan and its metabolites on sciatic nerve blockades of motor function, proprioception, and nociception were evaluated. Lidocaine was used as control. We found that dextromethorphan and its metabolites produced dose-related local anaesthetic effects on sciatic nerve blockades of motor function, proprioception, and nociception. The ranks of potencies were lidocaine>dextromethorphan>3-methoxymorphinan>dextrorphan (P<0.01 for each comparison). Under an equi-potent basis, dextrorphan and 3-methoxymorphinan had durations of actions longer than that of lidocaine (P<0.05 for each comparison). Co-administration of dextromethorphan or its metabolites with lidocaine produced an additive effect on sciatic nerve blockades. In conclusion, dextromethorphan and its metabolites - 3-methoxymorphinan and dextrorphan- had a local anaesthetic effect on sciatic nerve blockades of motor function, proprioception and nociception with durations of actions longer than that of lidocaine. Co-administration of dextromethorphan and its metabolites produced an additive effect on sciatic nerve blockades.

The antinociceptive and anti-inflammatory effects of five depot formulations of ketorolac propyl ester in rats.

BACKGROUND: Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these formulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control. METHODS: Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 micromol/kg on Sprague-Dawley rats treated with intraplantar carrageenin. RESULTS: Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation. CONCLUSIONS: All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.

The antinociceptive and anti-inflammatory effects of a long-acting depot formulated ketorolac in rats.

BACKGROUND: Currently, no long-acting nonsteroidal anti-inflammatory drug is available clinically for the treatment of long-lasting pain. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects and duration of action of a novel depot formulation of ketorolac benzyl ester in sesame oil. METHODS: Two studies in Sprague-Dawley rats were carried out. In study 1, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine were evaluated. In study 2, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac benzyl ester were evaluated. The antinociceptive effect was evaluated using the paw pressure test, whereas the anti-inflammatory effect was evaluated by the paw edema test. RESULTS: Intramuscular ketorolac tromethamine at 24, 80, and 240 micromol/kg (in saline) produced significant antinociceptive and anti-inflammatory effects with duration of action around 6 to 8 h. Ketorolac benzyl ester at a dose of 240 micromol/kg (in oil) produced significant long-acting antinociceptive and anti-inflammatory effects with duration of action of 56 h. CONCLUSIONS: Intramuscular injection of ketorolac benzyl ester (in sesame oil) in rats produced antinociceptive and anti-inflammatory effects which were 7-fold longer in duration of action than ketorolac tromethamine (in saline).