Evolution of the Anticonvulsant Activity of α-Terpineol

Abstract

α-Terpineol, a monoterpenoid alcohol, was investigated for its anticonvulsant activity. This compound increased the latency to convulsions induced by pentylenetetrazole at doses of 100 and 200 mg/kg and decreased the incidence of hindlimb extension produced by MES in a dose-related manner at doses of 200 and 400 mg/kg.

Keywords:

• Anticonvulsant activity
• essential oil
• monoterpene
• α-terpineol

Introduction

Many essential oils are known to have anticonvulsant activity (Almeida et al., 2003), probably due to terpenes that are the main constituents. This notion is supported by previous studies that showed that some monoterpenes present in many essential oils possess anticonvulsant activity in animal experiments, such as linalool (Elisabetsky et al., 1995), citral, β-myrcene, and limonene (Viana et al., 2000).

α-Terpineol is a volatile monoterpenoid alcohol and component of the essential oils of several species of plants (Dagne et al., 2000; Golshani et al., 2004; Raina et al., 2004). This compound is widely used in the perfumery, cosmetic, and soap industries. It is also used as a scenting agent in household products (e.g., disinfectant sprays) (Craveiro et al., 1981). The current investigation was carried out to evaluate the anticonvulsant activity of α-terpineol.

Materials and Methods

Animals

Male Swiss mice (28–35 g) were obtained from our research animal house. The animals were maintained at constant room temperature (27 ± 1°C) and on a 12/12 h light-dark cycle (light from 0600 to 1800 h), with free access to food and water. All behavioural observations were conducted between 1300 and 1800 h.

Drugs

Pentylenetetrazole (PTZ), Phenobarbital, and diazepam (DZP) were purchased from Sigma Chemical Co. St. Louis, M., (USA). (±)-α-Terpineol was purchased from Dierberger (João Pessoa, Brazil) and dissolved in 5% Tween 80 as an emulsion.

Anticonvulsant screening

Pentylenetetrazole-induced convulsions

Mice were divided into four groups. The first group served as control and received Tween 80, and the second group was treated with DZP (4 mg/kg). The remaining groups received an injection of α-terpineol at doses of 100 and 200 mg/kg. Thirty minutes after drug administration, the mice were treated with PTZ (i.p.) at a dose of 60 mg/kg and observed for at least 15 min to detect the occurrence of the first episode of forelimb clonus (Swinyard et al., 1989).

Maximal electroshock test

Mice were divided into five groups. The first group served as control and received Tween 80, and the second group was treated with phenobarbital (25 mg/kg). The remaining groups received an injection of α-terpineol at doses of 100, 200, or 400 mg/kg of α-terpineol (i.p.). Thirty minutes after treatment, mice received an electroconvulsive shock (130 V, 150 pulses/s, 0.5 s) through auricular electrodes to induce tonic hindlimb extension (THE). The number of animals showing tonic convulsions, characterized by the presence of THE, was observed (Oliveira et al., 2001).

Statistical analysis

The results were analyzed by means of variance analysis followed by Dunnet's test or Fisher's exact test. A probability level of 0.05 was accepted as significant.

Results

Two experiments were carried out on the effects of α-terpineol on anticonvulsant activity.

Pentylenetetrazole-induced convulsions

In the first experiment, α-terpineol increased the latency time of convulsions induced by PTZ at the dose of 200 mg/kg, using as drug pattern DZP (4 mg/kg) compared with control (Figure 1).

Figure 1 Effect of α-terpineol on PTZ-induced convulsive seizures in mice.

Maximal electroshock test

α-Terpineol produced a dose-dependent protection against the maximal electroshock seizure pattern test, reaching maximum at 400 mg/kg (Figure 2). The reference drug phenobarbital (25 mg/kg) also produced a significant protection.

Figure 2 Effect of α-terpineol in the maximal electroshock test in mice.

Discussion

The anticonvulsant activity of α-terpineol was investigated in mice using chemical (pentylenetetrazole-induced convulsions) and physical (maximal electroshock test) animal models. As shown in Figure 1, α-terpineol at doses of 100 and 200 mg/kg was effective to induce a significant increase of the latency in PTZ-induced convulsions. In this model, DZP (4 mg/kg), a standard drug, produced a greater increase of the latency. Complete protection against convulsions was observed in the maximal electroshock test. Interestingly, the α-terpineol was also effective in preventing tonic convulsions showing dose-dependent protection. As shown in Figure 2, at dose of 400 mg/kg, it afforded 100% protection, and phenobarbital (25 mg/kg) was used as a positive control.

The fact that α-terpineol is a relatively common monoterpene and is present in many aromatic and medicinal plants shows the importance of studying the potential of this compound as an anticonvulsant drug. The current study provides evidence that α-terpineol has anticonvulsant activity, as shown in chemical and physical tests.