Alcamidas: uma revisão bibliográfica de seu potencial anticonvulsivante

Abstract

Epilepsy is a severe and chronic neurological disorder characterized by recurrent seizures resulting from excessive electrical discharges in neurons. Medication resistance, or refractoriness, poses a significant challenge, with approximately one-third of patients failing to achieve seizure control despite trials with at least two appropriate medications. Medicinal cannabis, particularly cannabidiol (CBD), has demonstrated promising potential as a treatment due to its therapeutic properties and favorable safety profile, characterized by rare side effects and a low risk of dependence. However, the legal approval of cannabinoid compounds, such as CBD, faces significant obstacles in Brazil, limiting access to these innovative treatments. Consequently, the search for new therapeutic alternatives remains a critical area of research. Alkamides, also known as alkylamides, are secondary metabolites found in various plants. These compounds exhibit a wide range of biological activities, including antimicrobial, antiviral, analgesic, and immunomodulatory properties. Their structural similarity to anandamide, an endogenous neurotransmitter that modulates the Endocannabinoid System through CB1 and CB2 receptors, suggests their potential as ligands for cannabinoid receptors. This characteristic positions alkamides as a promising alternative for the treatment of neurological conditions, such as epilepsy, particularly in contexts where medicinal cannabis faces legal restrictions. In the present study, four articles were analyzed, encompassing a total of six in vivo studies, one in vitro study, and one in silico study, published between 2014 and 2024. These studies demonstrated that alkamides exert anticonvulsant effects through multiple mechanisms, including modulation of the Endocannabinoid System via interaction with CB2 receptors; blockade of ion channels, such as sodium and calcium channels, which are associated with neuronal activity; enhancement of GABAergic activity, increasing neuronal inhibition; modulation of cholinergic receptors, reducing neuronal excitability; inhibition of TRPV1 receptors, which are linked to epileptogenesis. Therefore, alkamides represent a promising therapeutic approach for the treatment of epilepsy, particularly in cases refractory to conventional medications, owing to their multifaceted mechanisms of action. Further research is essential to fully explore their clinical potential and and allow them to appear as candidates for phytopharmaceuticals.