Comparative analgesic and antiinflammatory investigation of oxygenated monterpenes

Monoterpenes are member of a large and diverse group of molecules found in nature and also obtained by synthesis. Carvacrol, thymol, (+)-terpinen-4-ol, (+)-alpha-terpineol, 1,8-cineole, 1,4-cineole were subjects of this study as oxygenated monoterpenes to investigate analgesic and antiinflammatory actions. o-Cresol and m-cresol were also added into the test compounds in order to compare the actions of these oxygenated monoterpenes due to the initial hypotheses of their inactivity. Tail-clip and tail-immersion tests were used for analgesic tests and formalin induced inflammation was used for antiinflammatory activity. Test substances (10, 50 and 100 mg/kg i.p) were solved and diluted in sunflower oil but due to contradictory results, DMSO was used throughout the study. Naloxone and ruthenium red were used to investigate possible opioid and TRP mechanisms of the observed actions. Carvacrol was tested on healthy and inflammed isolated mouse distal colon against acetylcholine induced contractions. Carvacrol, thymol, (+)-alpha-terpineol and 1,8-cineole exhibited analgesic actions, carvacrol being the most active of the test compounds. Analgesic actions of active compounds were antagonized by ruthenium red and analgesic activity of (+)-alpha-terpineol was also antagonized by naloxone. Carvacrol, thymol, (+)-terpinen-4-ol, (+)-alpha-terpineol, 1,8-cineole and 1,4-cineole reduced formaline-induced inflammation which were antagonized or attenuated by ruthenium red. (+)-Terpinen-4-ol was active on formaline induced inflammation but inactive on analgesic tests. In contrast to our hypothesis, o-cresol was active and ruthenium red augmented the actions of o- and m-cresols. Carvacrol inbibited acetylcholine induced contractions only on healthy but not on inflammed distal colon segments. Our results suggests that in addition to carvacrol, thymol, 1,8-cineole, (+)-alpha-terpineol and (+)-terpinen-4-ol, o-cresol also may interact with TRP channels exerting antiinflammatory actions. It was concluded that due to the chemical properties of the test compounds, the position of hydroxyl group and specially the presence of isopropyl group were important for the observed actions of the test compounds.