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)

Agmatine is an endogenous amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC), and metabolized to putrescine by agmatinase. Exogenously administered agmatine has several biological actions including its ability to potentiate morphine analgesia and block symptoms of morphine tolerance/withdrawal in rats. To investigate the role of endogenous agmatine in this action, we sought to determine whether chronic exposure to morphine and induction of withdrawal modulate the synthesis of agmatine in rat brain and other tissues. Exposure of rats to morphine for three days significantly decreases the activity of ADC and the levels of agmatine in rat liver, kidney, brain, aorta and intestine with no changes in agmatinase activity. The precipitation of withdrawal syndrome by injecting naloxone further decreases ADC activity and agmatine levels in these tissues. We conclude that endogenous agmatine may play an important role in regulating morphine tolerance/dependence and withdrawal symptoms.
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PMID:Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues. 1213 15

Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, alpha2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.
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PMID:Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence. 1702 65

Agmatine is an endogenous amine that is synthesized following the decarboxylation of L-arginine by arginine decarboxylase. Agmatine exists in mammalian brain and has been proposed as a neurotransmitter and/or neurotransmodulator. Agmatine binds to several targets and is considered as an endogenous ligand for imidazoline receptors. This review, mainly based on our research work in the past decade, focused on the modulations by agmatine action on imidazoline receptors to opioid analgesia, tolerance and dependence, and its possible neurochemical mechanisms. We went on to propose that agmatine and imidazoline receptors constitute a novel system of modulating opioid functions.
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PMID:Agmatine and imidazoline receptors: their role in opioid analgesia, tolerance and dependence. 1765 50

Agmatine is an amine formed by the decarboxylation of l-arginine by the enzyme arginine decarboxylase. The fact that exogenous agmatine modulates morphine analgesia and dependence raises the question of whether the biosynthesis of endogenous agmatine is regulated during chronic pain. As a first step to understand the biological role of agmatine in human neurological and psychiatric conditions, this study was aimed to determine the levels of cerebrospinal fluid (CSF) agmatine in normal individuals. The levels of agmatine in the CSF and blood were measured by high-performance liquid chromatography (HPLC) method. Samples of CSF and blood were collected from a total of 10 participants for this study. The CSF agmatine levels ranged from 24.3 to 54.0 ng/mL, whereas the plasma agmatine levels were from 8.4 to 65.1 ng/mL. The mean values with standard error for blood and CSF agmatine were 33.8 +/- 16.6 and 40.4 +/- 9.1, respectively. The statistical analysis of these 10 samples indicated no correlation between blood and CSF samples (r = .29); however, removing one outlier improved the correlation (r = .6). From this study, the authors conclude that human CSF agmatine levels can be measured by HPLC with precision and that a possible correlation exists between plasma and CSF agmatine levels. This study provides basis for future studies in human chronic pain conditions.
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PMID:Agmatine levels in the cerebrospinal fluid of normal human volunteers. 1929 53