Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported antitussive effects of naltrindole (NTI), a typical delta opioid receptor antagonist, in a rat model. The ED50 values of NTI by intraperitoneal and peroral injections were 104 microg/kg and 1840 microg/kg, respectively, comparable to those of codeine. Codeine, one of the most reliable centrally acting antitussive drugs, has micro agonist activity and thus the same side effects as morphine, e.g., constipation, dependency, and respiratory depression. Because NTI is a delta opioid antagonist, its derivatives have potential as highly potent antitussives, free from the mu opioid agonist side effects. We attempted to optimize the NTI derivatives to develop novel antitussive agents. On the basis of the studies of structure-antitussive activity relationships of alkyl substituted NTI derivatives, we designed NTI derivatives with extra ring fused structures. As a clinical candidate, we identified a highly potent new compound, (5R,9R,13S,14S)-17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5',6'-dihydro-3-methoxy-4'H-pyrrolo[3,2,1-ij]quinolino[2',1':6,7]morphinan-14-ol (5b) methanesulfonate (TRK-850) which was effective even by oral administration (ED50 6.40 microg/kg).
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PMID:Structure-antitussive activity relationships of naltrindole derivatives. Identification of novel and potent antitussive agents. 1863 71

Several studies have implicated codeine use in the aetiopathogenesis of male infertility. The purpose of this study was to investigate the role of HER2, Ki67, oestrogen and p53/Bcl-2 signaling pathways and the possible outcome of codeine cessation on codeine-induced reproductive toxicity. Thirty adult male Wistar rats of comparable ages and weights were randomly allocated into 5 groups. The control animals received distilled water per os (p.o), while animals in the low-dose (LDC) and high dose (HDC) codeine-treated groups received 2 and 5 mg/kg/day of codeine respectively p.o for 6 weeks. The animals in the low-dose codeine recovery (LDC-R) and high-dose codeine recovery (HDC-R) groups received treatment as LDC and HDC respectively followed by another drug-free six weeks, recovery period. Cessation of codeine exposure led to a partial reversal of codeine-induced poor sperm quality, reduced litter size and weight, increased oxidative testicular injury, testicular apoptosis, and testicular DNA damage caused by codeine administration. Codeine-induced gonado-spermotoxicity was associated with a reduction of circulatory testosterone, suppression of testicular HER2, Ki67, and Bcl-2 expression, down-regulation of oestrogen signaling, and upregulation of testicular caspase 3 activities and p53 signaling pathway. Conclusion: Upregulation of oestrogen signaling associated with enhanced testicular HER2 and Ki67 expression during the recovery period is seemingly beneficial in protecting against codeine-related testicular injury and infertility.
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PMID:In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway. 3329 12