Formalin assay parameters differ in confirming the antinociceptive mechanism of domperidone in mice.

Domperidone, a prokinetic drug with minimal extrapyramidal side-effects was investigated for its antinociceptive response in mice using formalin assay procedure. Two parameters namely the pain score and the time spent by the animal in licking/biting the formalin injected paw were considered. Domperidone (1, 2.5 or 5 mg/kg; ip) injected 15 min prior to formalin effectively reduced the pain score bringing it to zero at the 15th minute and was also effective till 30 min but to a lesser degree. This effect of domperidone (2.5 mg/kg) was significantly attenuated in naloxone pretreated mice indicating a partial role for opioid pathways. In the other parameter i.e. time spent in licking/biting, domperidone in all the doses employed failed to modify significantly the same by the animal in the early phase. In contrast, a dose related inhibition of the time spent was recorded in the late phase. Besides, a trend towards the enhancement of the inhibitory effect of domperidone (2.5 mg/kg) in the late phase was noticed in naloxone pretreated mice. Possibly, the peripheral analgesic mechanisms may play a role in this response since the late phase was considered akin to inflammation. The results confirm the antinociceptive effect of domperidone and suggest that caution be exercised while selecting the parameters when formalin assay is employed.

Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of metoclopramide.

Metoclopramide, a prokinetic drug, has been documented to produce antinociceptive response in animal models through opioid pathways. Morphine has been shown to act through ATP sensitive potassium channels (KATP) to produce antinociceptive response. However, such a possibility has not been examined for metoclopramide. The present study investigated this using pharmacological tools. Acetic acid induced abdominal constriction assay procedure was utilized to assess antinociception. The results confirmed that metoclopramide has antinociceptive response. Glibenclamide, a KATP channel blocker, pretreatment antagonized this response. Where as, in minoxidil pretreated animals, metoclopramide elicited an enhanced antinociceptive response. Glibenclamide and minoxidil, which are known KATP channel blocker and opener respectively, interfered with metoclopramide antinociception. These finding are suggestive of a role for KATP channels in metoclopramide antinociception in mice.

Pharmaco-economic analysis of psychotropic drugs.

OBJECTIVES: To analyse cost and adverse reactions of psychotropic drugs for their cost-effective use. METHODS: Four hundred and sixty nine psychotropic formulations from CIMS, June 1998 were evaluated for (a) extent of variation in retail price for same strength and dosage form, (b) role of number of companies manufacturing the same formulation and (c) companies pricing their product at price less than average of maximum and minimum price in relation to number of products marketed by them. The side effects of antipsychotic and antidepressant drugs were graded for their severity and cumulative side effects score. Side effect index and cost index were calculated on relative basis and their product was used as cost benefit index. RESULTS: Fifty per cent of psychotropic drugs had less than 100% price variation with highest of 2049% for risperidone 4 mg tablets. A direct relationship existed between the drug cost and price variation wherever the variation crossed 200%. Similar trend was noticed between the minimum price variations and the number of companies marketing the product. There was no appreciable relationship between number of products marketed and pricing by the manufacturer. Cumulative side effect score was lowest (10) for trifluoperazine and pimozide and highest (15) for risperidone amongst antipsychotic drugs, whereas amongst antidepressants fluoxetine had lowest (1.75) and amitryptyline had highest (28.5) cumulative side effect score. CONCLUSION: One has to be more careful while selecting a brand of a drug when price variation is more (200-2049%). Trifluoperazine (1.0) and fluoxetine (1.7) were found to be most economical with better cost benefit index compared to thioridazine (494.2) and clomipramine (113.0) in their respective groups. Thus our analysis provides basic information regarding cost effective therapy with psychotropic drugs.