Effects of Alprazolam, Zolpidem and Zopiclone, and of chronic inflammation on peripheral experimental algesia in Wistar rats.

In the literature, there are some data which indicate that benzodiazepines and other chemical compounds with the same mechanism of action (Diazepam, Chlordiazepoxide, Lorazepam, Zopiclone, etc.) also have other effects. We investigated the effects of experimental chronic inflammation under the administration of some tranquilizers and hypnotics on peripheral algesia induced in rats by "writhing test". Chronic inflammation was induced by "cotton wool granuloma" technique. The "writhing test" consisted in intraperitoneal injection of an irritant agent (acetic acid 0.0025%, 0.4 mL). The animal reacts with a characteristic stretching behavior called writhing. A writhe is indicated by stretching of the abdomen with simultaneous stretching of at least one hind limb. Then, the animals were placed individually into glass beakers and 5 minutes were allowed to elapse. The rats were then observed for a period of 10 minutes and the number of writhes is recorded for each animal. Three drugs were administered by gastric probe: Alprazolam 1 mg/kg, Zolpidem 10 mg/kg and Zopiclone 10 mg/kg. Alprazolam is a triazolobenzodiazepine derivative used as a tranquilizer. Zolpidem is an imidazopyridine with marked sedative-hypnotic effect and it has the same mechanism of action like benzodiazepines. Zopiclone is a cyclopyrrolone with sedative-hypnotic effect used as hypnotic and acts like benzodiazepines. After that, the animals were sacrificed and the weight of cotton wool granuloma was determined. In the same time, the histopatological aspect of granulomatous inflammation was studied. It was found that experimental proliferative inflammation under the action of these drugs was accompanied by a peripheral analgesic activity in "writhing test". The mechanisms of these effects are not fully elucidated. Some explanations are: they act as agonists or antagonists on algesia and inflammation mediators and they have a stimulating effect on peripheral ω3-benzodiazepine receptors ("peripheral-type" receptors).