Linalool blocks excitability in peripheral nerves and voltage-dependent Na+ current in dissociated dorsal root ganglia neurons.
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.
Leal-Cardoso
José Henrique
JH
Laboratory of Electrophysiology, Superior Institute of Biomedical Sciences, Campus of Itaperi, State University of Ceará, Fortaleza, CE, Brazil. lealcard@gmail.com
da Silva-Alves
Kerly Shamyra
KS
Ferreira-da-Silva
Francisco Walber
FW
dos Santos-Nascimento
Tiago
T
Joca
Humberto Cavalcante
HC
de Macedo
Flávio Henrique Pequeno
FH
de Albuquerque-Neto
Pedro Militão
PM
Magalhães
Pedro Jorge Caldas
PJ
Lahlou
Saad
S
Cruz
Jader Santos
JS
Barbosa
Roseli
R
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*
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D015222:Sodium Channels; C018584:linalool