Risk factors for diaphragmatic dysfunction in mechanically ventilated patients: a systematic review and meta-analysis.

The repertoire of diseases that need better and cheaper treatment remains large. This has stimulated the search for new medicines, and for that purpose, the scientific community has been giving increasing attention to terpenes and terpenoids. This is because several of them could be easily found as natural constituents of essential oils [,]. This is also because of their pharmacological activities and therapeutic potentialities [,]. From the pharmacological point of view, they have been described as antispasmodic; antinociceptive and analgesic [,,]; antihypertensive [,], anti-inflammatory [,,,], anesthetic [], vasorelaxant [,], gastroprotective [,,], and antineoplastic [,,], including perillyl alcohol (POH) for treatment of the very aggressive cancer glioblastoma [,,,,,]. One trend of the pharmacology of terpenes and terpenoids that has raised increased interest is the molecular structure–activity relationship [,]. Terpenes and terpenoids are volatile substances of small molecular weight, usually very lipophilic. One radical that could have significant implications on the lipophilicity/hydrophilicity of the molecule is the hydroxyl [,,]. Indeed, some studies have demonstrated the importance of the hydroxyl group of terpenoids in modulating pharmacological activities [,,,]. The presence and the position of polar functional groups, such as the -OH, have been demonstrated to be critical factors that can influence the pharmacological potency and efficacy of these molecules [,]. Investigation of our laboratory on the influence of the hydroxyl group on the inhibitory effect of POH, carveol (CV), and limonene (LM) () on smooth muscle contraction demonstrated that the presence and the position of the hydroxyl group may alter the pharmacological potency []. The previous investigation [] used POH and CV, with the hydroxyl group attached to a primary and secondary carbon atom, respectively, and LM, without hydroxyl group. The pharmacological potencies differed significantly and were POH > CV > LM []. The inhibitory effect of the three substances was interpreted to be mainly through the effect on the voltage-dependent Ca channel. One important aspect of the contribution of the hydroxyl group to the pharmacological effects of monoterpenes is its influence on nerve excitability. Peripheral nerves are composed of distinct fiber populations that differ in their electrophysiological properties and susceptibility to pharmacological modulation. Recording the compound action potential (CAP) provides a simple and reliable electrophysiological approach for assessing changes in the excitability of these different types of nerve fibers. Therefore, to investigate whether perillyl alcohol (POH), carveol (CV), and limonene (LM) modulate nerve excitability, and to determine the extent to which the hydroxyl group influences the pharmacodynamic parameters underlying this effect, we evaluated their actions on the compound action potential of the mouse sciatic nerve.