title: Linalool blocks excitability in peripheral nerves and voltage-dependent Na+ current in dissociated dorsal root ganglia neurons.
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 (IC(50) was 0.78+/-0.04 mM). At 0.8mM, it reversibly increased rheobase and chronaxy (from 3.2+/-0.1 V and 52.4+/-4.1 micros to 4.2+/-0.3 V and 71.2+/-5.5 micros (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.
authors.affiliation: Laboratory of Electrophysiology, Superior Institute of Biomedical Sciences, Campus of Itaperi, State University of Ceará, Fortaleza, CE, Brazil. lealcard@gmail.com
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Leal-Cardoso
authors.forename: Kerly Shamyra
authors.initials: KS
authors.lastname: da Silva-Alves
authors.forename: Francisco Walber
authors.initials: FW
authors.lastname: Ferreira-da-Silva
authors.forename: Tiago
authors.initials: T
authors.lastname: dos Santos-Nascimento
authors.forename: Humberto Cavalcante
authors.initials: HC
authors.lastname: Joca
authors.forename: Flávio Henrique Pequeno
authors.initials: FH
authors.lastname: de Macedo
authors.forename: Pedro Militão
authors.initials: PM
authors.lastname: de Albuquerque-Neto
authors.forename: Pedro Jorge Caldas
authors.initials: PJ
authors.lastname: Magalhães
authors.forename: Saad
authors.initials: S
authors.lastname: Lahlou
authors.forename: Jader Santos
authors.initials: JS
authors.lastname: Cruz
authors.forename: Roseli
authors.initials: R
authors.lastname: Barbosa
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000080462:Acyclic Monoterpenes; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D015222:Sodium Channels; C018584:linalool