An In Silico Approach to Exploring the Antinociceptive Biological Activities of Linalool and its Metabolites.

Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.

Computational Studies Applied to Linalool and Citronellal Derivatives Against Alzheimer's and Parkinson's Disorders: A Review with Experimental Approach.

Alzheimer's and Parkinson's are neurodegenerative disorders that affect a great number of people around the world, seriously compromising the quality of life of individuals, due to motor and cognitive damage. In these diseases, pharmacological treatment is used only to alleviate symptoms. This emphasizes the need to discover alternative molecules for use in prevention. Using Molecular Docking, this review aimed to evaluate the anti-Alzheimer's and anti-Parkinson's activity of linalool and citronellal, as well as their derivatives. Before performing Molecular Docking simulations, the compounds' pharmacokinetic characteristics were evaluated. For Molecular Docking, 7 chemical compounds derived from citronellal, and 10 compounds derived from linalool, and molecular targets involved in Alzheimer's and Parkinson's pathophysiology were selected. According to the Lipinski rules, the compounds under study presented good oral absorption and bioavailability. For toxicity, some tissue irritability was observed. For Parkinson-related targets, the citronellal and linalool derived compounds revealed excellent energetic affinity for α-Synuclein, Adenosine Receptors, Monoamine Oxidase (MAO), and Dopamine D1 receptor proteins. For Alzheimer disease targets, only linalool and its derivatives presented promise against BACE enzyme activity. The compounds studied presented high probability of modulatory activity against the disease targets under study, and are potential candidates for future drugs.

Post-learning caffeine administration improves 'what-when' and 'what-where' components of episodic-like memory in rats.

Episodic-like memory (ELM) consists in the capacity of nonhuman animals to remember 'where' and 'when' a specific episode occurred ('what'). Previous studies have showed that Wistar rats can form an ELM, but not after a 24 h retention delay. On the other hand, it has been demonstrated that caffeine can improve episodic memory consolidation in humans. Therefore, we verified whether acute post-sample caffeine administration could improve ELM consolidation in Wistar rats, as well if it could be related to neurochemical changes in the prefrontal cortex and hippocampus - regions related to episodic-like memory processing. 46 Male Wistar Rats, approximately 3 months-old, were divided into four groups as follows: untreated (n = 11), saline (n = 11), caffeine 10 mg ∕kg i.p (n = 12); caffeine 15 mg∕kgi.p (n = 12) and tested in WWWhen/ELM task. The animals treated with caffeine in different dosages (10 mg/kg and 15 mg/kg) discriminated temporally and spatially the objects, respectively. These groups also showed a dopamine renewal rate in the hippocampus, suggesting that there was an increase in the turnover compared with the groups with no caffeine administration. We can conclude that caffeine leads to an improvement in the consolidation of the temporal ('what-when') and spatial ('what-where') aspects of episodic-like memory.