Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extrahepatic expression of UDP-glucuronosyltransferases (UGTs) is important in the detoxification of a number of endogenous and exogenous compounds, including 5-hydroxytryptamine and morphine. Studies were designed to investigate the extrahepatic expression of human UGTs using RT-PCR techniques and to determine the UGTs involved in the glucuronidation of 5-hydroxytryptamine. Human UGT2B7 expression was found in the human liver, kidney, pancreas, and brain, while UGT1A6 expression is found in the liver, kidney, and brain. This is the first observation of UGTs present in the human central nervous system. Using glucuronidation assays, a significant amount of 5-hydroxytryptamine glucuronide was found to be catalyzed by UGT1A6. These studies suggest that UGT2B7 may play an important role in the overall contribution of morphine analgesia by serving to generate the potent morphine-6-O-glucuronide in situ. UGT1A6 could play an important role in the glucuronidation of 5-hydroxytryptamine in vivo, therefore terminating the actions of the neurotransmitter.
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PMID:Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate. 1022 50

Glucuronide conjugates represent one of the major types of naturally occurring phase 2 metabolites of xenobiotics and endobiotics. The process underlying their formation, glucuronidation, is normally considered detoxifying, because glucuronides usually possess less intrinsic biological or chemical activity than their parent aglycones and they are rapid excreted. However, a number of glucuronide conjugates are known that are active and may contribute to pharmacological activities or toxicities associated with their parent compounds. These include two classes of glucuronides with electrophilic chemical reactivity (N-O-glucuronides of hydroxamic acids and acyl glucuronides of carboxylic acids) and several types of glucuronides that impart biological effects through non-covalent interactions (morphine 6-O-glucuronide, retinoid glucuronides, and D-ring glucuronides of estrogens). Glucuronides may thus contribute to clinically significant effects, including environmental arylamine-induced carcinogenesis, drug hypersensitivity and other toxicities associated with carboxylic acid drugs, morphine analgesia, and cholestasis from estrogens. This review summarizes the rat and human UDP-glucuronosyltransferases that may be involved in the formation of bioactive glucuronides, including their substrate- and tissue-specificity and genetic and environmental influences on their activity. This knowledge may be useful for enhancing the therapeutic efficacy and minimizing the risk of adverse effects associated with xenobiotics that undergo bioactivating glucuronidation reactions.
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PMID:Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. 1115 40

The influence of long-term nifedipine administration on the antinociceptive activity of acetaminophen on hexobarbital sleeping time and liver monooxygenase and synthetase activities was studied in male albino mice. Nifedipine was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. The nociceptive response was determined by the acetic acid writhing test. There was no significant difference in the antinociceptive effect of acetaminophen after treatment with nifedipine for 14 days. Nifedipine caused enzyme induction, which was demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine-N-demethylase (EMND), aniline-4-hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), UDP-glucuronyl transferase (UDPGT), glutathione-S-transferase (GST) and NADPH-cytochrome c reductase activity and increased content of cytochrome P450 and cytochrome b5. It is assumed that this effect of nifedipine on acetaminophen analgesia is associated with the changes (acceleration) in acetaminophen metabolism in the liver after repeated administration of the drug.
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PMID:Effect of long-term multiple nifedipine administration on the antinociceptive activity of acetaminophen. 1195 44

The chemical structures of morphine and its metabolites are closely related to the clinical effects of drugs (analgesia and side-effects) and to their capability to cross the Blood Brain Barrier (BBB). Morphine-6-glucuronide (M6G) and Morphine-3-glucuronide (M3G) are both highly hydrophilic, but only M6G can penetrate the BBB; accordingly, M6G is considered a more attractive analgesic than the parent drug and the M3G. Several hypotheses have been made to explain these differences. In this review we will discuss recent advances in the field, considering brain disposition of M6G, UDP-glucoronosyltransferases (UGT) involved in morphine metabolism, UGT interindividual variability and transport proteins.
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PMID:Morphine metabolism, transport and brain disposition. 2219 38