Metabolic Products of Linalool and Modulation of GABAA Receptors

Abstract

Terpenoids are major subcomponents in aroma substances which harbor sedative physiological potential. We have demonstrated that various monoterpenoids such as the acyclic linalool enhance GABAergic currents in an allosteric manner in vitro upon overexpression of inhibitory α1β2 GABAA receptors in various expression systems. However, in plants or humans, i.e., following intake via inhalation or ingestion, linalool undergoes metabolic modifications including oxygenation and acetylation, which may affect the modulatory efficacy of the generated linalool derivatives. Here, we analyzed the modulatory potential of linalool derivatives at α1β2γ2 GABAA receptors upon transient overexpression. Following receptor expression control, electrophysiological recordings in a whole cell configuration were used to determine the chloride influx upon co-application of GABA EC10−30 together with the modulatory substance. Our results show that only oxygenated linalool metabolites at carbon 8 positively affect GABAergic currents whereas derivatives hydroxylated or carboxylated at carbon 8 were rather ineffective. Acetylated linalool derivatives resulted in non-significant changes of GABAergic currents. We can conclude that metabolism of linalool reduces its positive allosteric potential at GABAA receptors compared to the significant potentiation effects of the parent molecule linalool itself.

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved

“…9, 10 and 12 showed that flumazenil reversed the pharmacological response of EO in some important behavioral parameters, suggesting the possible involvement of GABA A receptors. These findings are in agreement with several pharmacological reports demonstrating that the sedative and anxiolytic potential of monoterpenes and sesquiterpenes appears to be mediated by GABA/benzodiazepine transmission (Granger et al, 2005;Rivera et al, 2014;Milanos et al, 2017;Sousa et al, 2015). Additionally, EO promoted no alteration in the motor coordination of the animals, being considered a satisfactory candidate for the development of new herbal medicines acting on CNS disorders.…”

Volatiles from <i>Acer truncatum</i> Flowers

“…Recent research showed that 3-Carene had sedative and analgesic, digestion and analgesic, antimicrobial effects. [19] Sinem Milanos [20] on the metabolism of Linalool and Linalool the regulation process has been studied and the results confirm that Linalool is well-known for its calming effect in the field of medicine. β-Pinene has obvious antibacterial activity in vitro [21], and Caryophyllene also has strong bacteriostatic action [22].…”

Aromatherapy in Patients with Cardiovascular Diseases: A Systematic Review

“…All 5 studies used aromatherapy with lavender essential oil in patients with cardiovascular diseases. 12,[15][16][17][18] The studies were published from 1992 to 2020. The sample size ranged from 60 to 135 patients, 15,17 and the mean age was 60 to 73 years.…”

“…The sample size ranged from 60 to 135 patients, 15,17 and the mean age was 60 to 73 years. 16,17 Three studies 12,15,16 included participants of both sexes, and 2 studies 17,18 included only women. Regarding the participants, 2 studies with reflexology (technique that stimulates different points on the feet).…”

“…5,11 Because of its anxiolytic and sedative properties, the Lavandula Officinalis species is recognized for its effective treatment of stress and anxiety. [10][11][12] The purpose of this review was to investigate the effects of the use of lavender essential oil on hemodynamic responses and emotional aspects in patients with cardiovascular diseases.…”