Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To address the different types of pain (e.g. acute, chronic, neuropathic) different classes of medications, mainly non-steroidal anti-inflammatory drugs and narcotics (opioids), are used. More specifically, the alleviation or treatment of moderate to severe pain states commonly invokes the use of opioids. Unfortunately, their chronic administration induces various undesirable side effects, such as for example physical dependence and tolerance. One strategy to overcome these major side effects and to prolong the antinociceptive efficiency of the applied drugs involves the creation of multifunctional compounds which contain hybridized structures. Combination of opioid agonist and antagonist pharmacophores in a single chemical entity has been considered and extensively investigated, but opioids have also been combined with other bioactive neurotransmitters and peptide hormones that are involved in pain perception (e.g. substance P, neurotensin, cholecystokinin, cannabinoids, melanocortin ligands, etc.). Such novel chimeras (also called designed multiple ligands or twin/triplet drugs), may interact independently with their respective receptors and potentially result in more effective antinociceptive properties. The designed multiple ligands presented in this work include opioid-non-opioid peptide dimer analogs, mixed peptidic- non-peptidic bifunctional ligands and dual non-peptidic dimers. The main focus herein is placed on the design and biological evaluation of these multiple opioid compounds, rather than the synthetic approach and preparation.
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PMID:Hybrid opioid/non-opioid ligands in pain research. 2344 81

The pain threshold effects of a neurotensin NT (8 - 13) dipeptide analog (dilept), morphine, and their combination have been studied using the tail flick test in rats. The animals of another experimental group were administered with morphine in increasing doses (10 - 20 mg/kg, i.p.) for 5 days in order to induce the state of dependence. The physical dependence on morphine was evaluated in the open-field test by monitoring 16 specific behavioral signs of withdrawal syndrome (WS) induced by the opioid receptor antagonist naloxone, after which the WS total index was calculated. It was established, that dilept (1.6 mg/kg, i.p.) produced a mild analgesic effect via increasing the pain threshold by 34% (p < 0.01), did not effect on the morphine analgesic effect, and decreased the expression of morphine WS by 29.1 and 37.5% (p < 0.01) after a single or subchronic administration, respectively. These behavioral effects of dilept were accompanied by normalization of dopamine and serotonin turnover in the hypothalamus, frontal cortex, and striatum of experimental animals.
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PMID:[Neurotensin NT (8- 13) dipeptide analog dilept increases the pain threshold and decreases the severity of morphine withdrawal syndrome in rats]. 2440 Mar 81