Introduction: indiscriminate use of opioids has increased dependency disorder and has been linked to half a million deaths worldwide in the last year. This justifies the exploration of alternative therapies for the treatment of addiction and overdose emergencies. Specific monoclonal antibodies have been produced for morphine and its metabolites for use in analytical identification tests in biological fluids from the experimental development of vaccines against these drugs. Objective: review scientific publications on monoclonal antibodies that identify morphine and its metabolites, to know its properties and the scope of its implementation in diagnostic tests. Method: systematic research of scientific literature in PubMed, ScienceDirect, SciELO and LILACS databases, published until September 2021, including articles on generation of monoclonal antibodies for morphine and its metabolites, and excluding those specialized only in molecular structure, point mutations and computational molecular dynamics. Results: 18 articles were identified where the production of 61 specific monoclonal antibodies for morphine and/or its metabolites was reported, and in which they characterized the specificity, sensitivity and/or detection range of the antibodies by evaluating 46 different substances, coupled to diagnostic tests. Discussion and conclusions: The production of monoclonal antibodies with high sensitivity and recognition for morphine and its metabolites has allowed their use in the development of sensitive analytical tests at affordable cost, which can be implemented in the clinical diagnosis and the surveillance of the use of these substances in the population.
BackgroundAlpha (α)-amidation of peptides is a mechanism required for the conversion of prohormones into functional peptide sequences that display biological activities, receptor recognition and signal transduction on target cells. Alpha (α)-amidation occurs in almost all species and amino acids identified in nature. C-terminal valine amide neuropeptides constitute the smallest group of functional peptide compounds identified in neurosecretory structures in vertebrate and invertebrate species.MethodsThe α-amidated isoform of valine residue (Val-CONH2) was conjugated to KLH-protein carrier and used to immunize mice. Hyperimmune animals displaying high titers of valine amide antisera were used to generate stable hybridoma-secreting mAbs. Three productive hybridoma (P15A4, P17C11, and P18C5) were tested against peptides antigens containing both the C-terminal α-amidated (–CONH2) and free α-carboxylic acid (−COO−) isovariant of the valine residue.ResultsP18C5 mAb displayed the highest specificity and selectivity against C-terminal valine amidated peptide antigens in different immunoassays. P18C5 mAb-immunoreactivity exhibited a wide distribution along the neuroaxis of the rat brain, particularly in brain areas that did not cross-match with the neuronal distribution of known valine amide neuropeptides (α-MSH, adrenorphin, secretin, UCN1-2). These brain regions varied in the relative amount of putative novel valine amide peptide immunoreactive material (nmol/μg protein) estimated through a fmol-sensitive solid-phase radioimmunoassay (RIA) raised for P18C5 mAb.ConclusionsOur results demonstrate the versatility of a single mAb able to differentiate between two structural subdomains of a single amino acid. This mAb offers a wide spectrum of potential applications in research and medicine, whose uses may extend from a biological reagent (used to detect valine amidated peptide substances in fluids and tissues) to a detoxifying reagent (used to neutralize exogenous toxic amide peptide compounds) or as a specific immunoreagent in immunotherapy settings (used to reduce tumor growth and tumorigenesis) among many others.
Introducción: por lo común, la adicción a las drogas se trata con psicoterapia y farmacología que evita la unión de las sustancias psicoactivas a receptores específicos en el cerebro. El resultado de estos tratamientos no ha sido del todo satisfactorio, por lo que el desarrollo de terapias más eficaces representa un reto constante para tratar las adicciones. Una alternativa a la farmacología antiadictiva es la vacunación activa dirigida contra las sustancias de abuso. Objetivo: esta revisión reúne la información disponible sobre los fundamentos y avances científicos en la generación de una terapia inmunológica, que coadyuve al tratamiento de la adicción a sustancias como la heroína-morfina, la cocaína, la nicotina y la anfetamina. Método: se consideraron los reportes científicos disponibles en PubMed –de 2005 a abril de 2017–, sobre los fundamentos, la metodología empleada, los estudios preclínicos y clínicos, y los resultados obtenidos en dichas investigaciones para generar vacunas contra las drogas. Resultados: las vacunas lograron mitigar los efectos producidos por las sustancias en los estudios preclínicos en modelos de estudio en animales; sin embargo, con pacientes humanos los resultados no han sido del todo satisfactorios. Discusión y conclusiones a pesar de los esfuerzos realizados por diferentes grupos de investigación y compañías farmacéuticas para generar vacunas terapéuticas contra el uso de diferentes drogas, ninguna ha alcanzado la fase III de estudios clínicos. En la actualidad, se continúa con los esfuerzos para lograr que las vacunas contra las adicciones alcancen su máxima eficiencia y eficacia, y contribuyan al tratamiento de la adicción a las drogas.
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