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Abstract: Linalool is a terpene that occurs as a major constituent of essential oils of many plants of widespread distribution. It possesses several biological and pharmacological activities, including depressant effects on the central nervous system and olfactory receptors. The present study investigated whether linalool affects the excitability of peripheral components of the somatic sensory system. We used sciatic nerve and preparations of intact and dissociated neurons of dorsal root ganglion for extracellular, intracellular and patch-clamp recordings. Linalool concentration-dependently (0.3–2.0mM) and reversibly blocked the excitability of the sciatic nerve. It inhibited peak-to-peak amplitude of the compound action potential (IC50 was 0.78±0.04mM). At 0.8mM, it reversibly increased rheobase and chronaxy (from 3.2±0.1V and 52.4±4.1μs to 4.2±0.3V and 71.2±5.5μs (n=5), respectively) and inhibited with greater pharmacological potency the amplitude of the compound action potential components corresponding to axons with slower velocity of conduction. In a similar concentration range (0.1–6mM), linalool concentration-dependently and reversibly blocked the generation of action potentials of intact dorsal root ganglion neurons without alteration of resting membrane potential and input resistance, and inhibited the voltage-gated Na+ current of dissociated dorsal root ganglion neurons. In conclusion, we demonstrated that linalool acts on the somatic sensory system with local anesthetic properties, since it blocked the action potential by acting on voltage-dependent Na+ channels. This finding is important in showing the potential usefulness of linalool as a pharmacotherapeutic agent. [ABSTRACT FROM AUTHOR]

Previously, we showed that the synthetic nitroderivative trans-4-methyl-β-nitrostyrene (T4MeN) induced vasorelaxant effects in rat isolated aortic rings. Here, we investigated the mechanisms underlying the cardiovascular effects of T4MeN in normotensive rats. In pentobarbital-anesthetized rats, intravenous (i.v.) injection of T4MeN (0.03-0.5 mg/kg) induced a rapid (onset time of 1-2 s) and dose-dependent bradycardia and hypotension. These cardiovascular responses to T4MeN were abolished by bilateral cervical vagotomy or selective blockade of neural conduction of vagal C-fiber afferents by perineural treatment of both cervical vagus nerves with capsaicin. Hypotension and bradycardia were also recorded when T4MeN was directly injected in the right, but not into the left ventricle. Furthermore, they were significantly reduced by i.v. pretreatment with capsazepine but remained unaltered by ondansetron or suramin. In conscious rats, the dose-dependent hypotension and bradycardia evoked by T4MeN were abolished by i.v. methylatropine pretreatment. In conclusion, bradycardiac and depressor responses induced by T4MeN has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. The transduction mechanism seems to involve the activation of vanilloid TRPV 1 , but not purinergic (P2X) or 5-HT 3 receptors located on vagal pulmonary sensory nerves., (Copyright © 2019 Elsevier B.V. All rights reserved.)