Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update: [review]

Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate (NMDA) transmission plays a pivotal role in the neuropathophysiology of schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising approaches to the treatment of schizophrenia. The aim of this article is to review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R). This review also includes a discussion and translation of neuroscience into schizophrenia therapeutics. Although the precise mechanism of action of minocycline in the brain remains unclear, there is evidence that it blocks the neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA signaling pathways. We, therefore, hypothesize that the effects of minocycline on the brain may be partially modulated by the NMDA-R or related mechanisms. Thus, we have included a review of minocycline neuroscience. The search was performed in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of glycine and D-cycloserine trials were conflicting regarding effectiveness on the negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a potential effect on negative symptoms and on cognitive deficits. Sarcosine data indicated a considerable improvement as adjunctive therapy. Finally, minocycline add-on treatment appears to be effective on a broad range of psychopathology in patients with schizophrenia. The differential modulation of NMDA-R neurosystems, in particular synaptic versus extrasynaptic NMDA-R activation and specific subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection. Thus, psychotropics modulating NMDA-R neurotransmission may represent future monotherapy or add-on treatment strategies in the treatment of schizophrenia.

Ketamina, una antigua droga que renace ante el dolor: parte I / Ketamine, and old drug coming back for pain management: part I

La Ketamina es una antigua droga usada como inductor anestésico, que debido a sus efectos adversos alucinatorios se subutilizó en las últimas décadas, pero debido al avance de las neurociencias y al conocimiento del dolor, renace como un potente medicamento analgésico (antihiperalgésico). Es un bloqueador no competitivo de los receptores NMDA, que son los receptores que se activan cuando el dolor es intenso, se postula que se podría utilizar para disminuir la percepción del dolor. es un neuromodulador del dolor y potenciador de la acción analgésica de los opioides. Los estudios clínicos han evidenciado su uso en el manejo del dolor postoperatorio dentro de una modalidad multimodal, con menor incidencia de náuseas y vómitos que al usar opioides solos y con reacciones adversas de tipo alucinatorias escasas. Las dosis ideales para los distintos tipos de cirugía, actualmente se basan en opiniones de expertos y se requieren mayores estudios. En dolor neuropático y en dolor por cáncer existe evidencia tipo IV, basadas en serie de casos que muestra ser útil. En tolerancia por opioides y en cronificación del dolor postoperatorio existen buenos estudios, pero aún no concluyentes. En conclusión, la ketamina es un fármaco útil, pero se debe conocer muy bien su farmacología para poder usarlo de manera segura y con un buen criterio clínico para el manejo del dolor moderado y/o intenso.

Ketamine is an old drug used in the induction of anesthesia that due to adverse hallucinatory effects has been under utilized during the past decades. However, the advances in neuroscience and a deeper knowledge of pain, ketamine is reborn as a strong analgesic (antihyperalgesic) aid. Ketamine is a non competitive blocker of NMDA receptors that are activated by severe pain and it could be used in pain reduction. Ketamine is a pain neuromodulator and enhancer of the opioids analgesic action. Clinicals trials showed it can be used in post surgery pain management in a number of ways with lessened side effects sunch as nausea and vomiting and scare hallucinatory effects compared to those caused by opioid treatment alone. the ideal dosage for different types of surgery now relies on the opinion of experts, however, further research is required. In neuropathic and cancer pain there is type IV evidence based on a number of cases that proves to be useful. Good trials, but not yet conclusive have been made in matters of tolerance to opioids and post surgery chronic pain. In conclusion, Ketamine is a useful drug, however, a deep knowledge of the same as well as good judgement are required for using it in moderate and/or severe pain management.