Monoterpenoid terpinen-4-ol inhibits voltage-dependent Na+ channels of small dorsal root ganglia rat neurons.

The monoterpenoid terpinen-4-ol (4TERP) is known to inhibit cell excitability, has low toxicity and important pharmacological activities, which are likely related to neural excitability, such as anti-inflammatory, antiepileptic and antinociceptive effects. However, the pharmacological characteristics and mechanisms underlying the effects of 4TERP on blockade of neural action potential are not completely elucidated. Since Na+ current (INa) through voltage-dependent Na+ channels (NaV) is a major mechanism for excitability, the present study investigated the pharmacological characteristics and mechanisms of the action of 4TERP on INa through NaV. For this aim, dissociated small neurons of dorsal root ganglia of adult rats were used for whole cell patch-clamp recordings. 4TERP concentration-dependently inhibits INa (IC50 0.8 ±â€¯0.3 mM; pharmacological efficacy 42.89 ±â€¯5.54%). 4TERP interfered with INa through a mechanism with various components, which includes predominantly channel pore block and sensitivity to frequency of use. In presence of 4TERP (3 mM), decreasing stimulation from 5 Hz to very low frequency (75 s of quiescence previously to stimulation) induced INa decrease to 65.17 ±â€¯5.86% of control. 4TERP also altered (left shift) voltage sensitivity of the steady state activation of NaV. Data are discussed aiming to interpret the importance of blockade of INa through NaV as participant of 4TERP-induced inhibition of membrane excitability.

Inhibitory effect of terpinen-4-ol on voltage-dependent potassium currents in rat small sensory neurons.

The biological and pharmacological activities of the terpenoid terpinen-4-ol (1), which include depressant effects in the central nervous system, are of potential therapeutic interest. In the present study, the effects of 1 on neuronal excitability and voltage-dependent K(+) currents in the somatic sensory system were investigated. Intact and dissociated neurons of rat dorsal root ganglia (DRG) were used for intracellular and patch-clamp recordings, respectively. In neurons of intact DRG, 1 caused concentration-dependent depolarization of the resting membrane potential and increased input resistance. 1 also inhibited action potentials (AP) and decreased AP parameters, with the exception of AP duration, which was increased. In dissociated DRG neurons, 1 partially blocked the total K(+) current in a concentration-dependent manner. 1 inhibited I(A), I(D), and I(K) with IC50 values of 3.2 ± 03, 0.7 ± 0.1, and 1.6 ± 0.7 mM, respectively. 1 did not shift either the steady-state activation or inactivation curves of I(A), I(D), and I(K) but reduced the decay time course of I(A). The alterations in DRG reported here are consistent with the inhibition of K(+) currents and might partially explain the effect of 1 on excitable tissues.