RESUMEN
Clavulanic acid (CLAV) is a non-antibiotic ß-lactam that has been used since the late 1970s as a ß-lactamase inhibitor in combination with amoxicillin, another ß-lactam with antibiotic activity. Its long-observed adverse reaction profile allows it to say that CLAV is a well-tolerated drug with mainly mild adverse reactions. Interestingly, in 2005, it was discovered that ß-lactams enhance the astrocytic expression of GLT-1, a glutamate transporter essential for maintaining synaptic glutamate homeostasis involved in several pathologies of the central nervous system (CNS). This finding, along with a favorable pharmacokinetic profile, prompted the appearance of several studies that intended to evaluate the effect of CLAV in preclinical disease models. Studies have revealed that CLAV can increase GLT-1 expression in the nucleus accumbens (NAcc), medial prefrontal cortex (PFC), and spinal cord of rodents, to affect glutamate and dopaminergic neurotransmission, and exert an anti-inflammatory effect by modulating the levels of the cytokines TNF-α and interleukin 10 (IL-10). CLAV has been tested with positive results in preclinical models of epilepsy, addiction, stroke, neuropathic and inflammatory pain, dementia, Parkinson's disease, and sexual and anxiety behavior. These properties make CLAV a potential therapeutic drug if repurposed. Therefore, this review aims to gather information on CLAV's effect on preclinical neurological disease models and to give some perspectives on its potential therapeutic use in some diseases of the CNS.
Asunto(s)
Antibacterianos , beta-Lactamas , Ácido Clavulánico/uso terapéutico , Ácido Clavulánico/metabolismo , Ácido Clavulánico/farmacología , Antibacterianos/uso terapéutico , beta-Lactamas/metabolismo , beta-Lactamas/farmacología , Núcleo Accumbens/metabolismo , Glutamatos/metabolismo , Glutamatos/farmacología , Transportador 2 de Aminoácidos Excitadores/metabolismoRESUMEN
Addiction is a chronic and potentially deadly disease considered a global health problem. Nevertheless, there is still no ideal treatment for its management. The alterations in the reward system are the most known pathophysiological mechanisms. Dopamine is the pivotal neurotransmitter involved in neuronal drug reward mechanisms and its neuronal mechanisms have been intensely investigated in recent years. However, neuroglial interactions and their relation to drug addiction development and maintenance of drug addiction have been understudied. Many reports have found that most neuroglial cells express dopamine receptors and that dopamine activity may induce neuroimmunomodulatory effects. Furthermore, current research has also shown that pro- and anti-inflammatory molecules modulate dopaminergic neuron activity. Thus, studying the immune mechanisms of dopamine associated with drug abuse is vital in researching new pathophysiological mechanisms and new therapeutic targets for addiction management.