Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System.

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.

Chemotherapy-induced neuropathic pain characteristics in Mexico's National Cancer Center pain clinic.

Introduction: Chemotherapy (CT) is one of the most commonly used pharmacological approaches in cancer treatment. However, CT induces damage to several tissues causing significant deleterious effects in cancer survivors being chemotherapy-induced neuropathic pain (CINP) among the most commonly reported. CINP is thought to be present in up to 68.1% of the patients within 1 month of receiving CT. Due to the fact that reliable statistic information is scarce in several Latin American countries' diagnosis and treatment of this side-effect may be delayed directly affecting patients. Therefore, the aim of the present study was to determine and present the incidence and features of CINP in patients with cancer attending the Pain Management Clinic at Mexicos' National Institute of Cancerology in Mexico City. Methods: We performed a retrospective, file-based analysis of all the patients treated in the Pain Management Clinic at the National Institute at Cancer in Mexico from January 2016 to January 2017. Results: CINP was found in 30.9% of the patients. The basal VAS was on average 2.5 upon arrival to the Pain Management Unit and 2.4 at the end of treatment (p>0.05). The patients with the highest risk of developing CINP were those treated with paclitaxel Odds ratio 8.3 (p<0.01), followed by platins OR 4 (p<0.01), vincristine OR 1.5 (p=0.01) and thalidomide OR 1.1 (p=0.01). Conclusion: Incidence of CINP was similar to previous reports; however, the number of variables related to this type of pain in our cohort may open a new line of research and highlight the importance of this particular issue to our health system. It is necessary to develop a mechanism to predict the risk of patients to suffer CINP and to search the mechanism to control and reduce the suffering related to the current treatments.

Ceftriaxone and clavulanic acid induce antiallodynia and anti-inflammatory effects in rats using the carrageenan model.

INTRODUCTION: Ceftriaxone (CFX) and clavulanic acid (CA) are 2 ß-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects. METHODS: The carrageenan (Carr) test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-α and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Both CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-α and IL-10 serum concentrations at different times. CONCLUSION: Our results provide evidence that both CFX and CA cause an analgesic effect on a Carr inflammatory pain model and that said analgesic effect differs between each ß-lactam molecule. Furthermore, this effect may be related to an anti-inflammatory effect of both molecules and a direct TNF-α and IL-10 serum concentration modulation.