Objective
In this programme, we harmonize the chemical, molecular, biochemical, pharmacological and clinical methodologies of different European teams to investigate basic mechanisms and therapeutic alternatives of drug dependence and nociception. In the first phase, we will investigate the role of the endogenous opioid system and their intracellular messengers in the pathophysiology of drug dependence and associated disorders. Two essential tools will be available to deal this objective: the mutant mice deficient in some proteins related to the intracellular response of the opioids (generated by partner 3) and the new inhibitors of enkephalin catabolism (synthesized by partners 4 and S). Mutant mice will be used to investigate the specific involvement in the development of these neurological disorders of cAMP-dependent pathway and gene expression. The different mutants now available and the generation of brain specific and inducible mutation for these proteins will allow penetrating deeper in the role of these intracellular messengers linked to the opioid system. A multidisciplinary approach (behavioural, partnerl; biochemical, partner 6; molecular, partner 3) will be used in this research.
The inhibitors of enkephalin catabolism recently design by partner 5 (RB 1000)represent an useful tool to complement the study at these neurological mechanisms. These inhibitors have a major advantage in comparison with previous compounds, e.g. they are active after oral administration. This improvement in the pharmacokinetic properties is a decisive step forward for evaluating their therapeutic perspectives. The results already obtained with RB 1000 in animals suggest promising therapeutic applications on pain relief and heroin addiction treatment. In a second phase, we propose to further characterize these pharmacological responses in order to obtain all the preclinical information necessary to start clinical trials in humans. Thus, the effects of RB 1000 in an objective physiological correlate of pain (nociceptive reflexes, partner 7) and its reinforcing properties (ability to be self-administered, partner 2) will be evaluated. Clinical studies on phase I and II are expected to be developed in the last part of this programme. For this purpose, a toxicological study is currently been performed with RB 1000 by an authorized laboratory that has already shown the absence of mutagenic, cancerogenic and major toxic effects after acute administration of this compound. The clinical research on phase I (partner 8) will provide information about the tolerability, safety, pharmacokinetic and pharmacodinamic properties of RB 1000 in human healthy volunteers. The phase II trials will give some indication of potential therapeutic activity of this compound for treatment of drug dependence (partner9) and pain relief (partner 8). These new compounds could particularly fill the still uncovered domain between non-opiate and classical opiate analgesics with a very interesting potential market. They could also have a therapeutic activity similar to methadone in the maintenance of heroin addicts without the side effects of opiates. Enkephalin catabolism inhibitors, Mutant mice, CREB, RB 1000, Analgesia, Drug dependence, Opiate, Affective disorders, Illicit drugs, Clinical trial.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology
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Coordinator
08003 BARCELONA
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.