Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence.
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.
Regunathan
Soundar
S
Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA. sregunathan@psychiatry.umsmed.edu
D000376:Agmatine / Q000627:therapeutic use*; D000698:Analgesia; D000701:Analgesics, Opioid / Q000009:adverse effects; D000818:Animals; D004361:Drug Tolerance; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000188:drug therapy / Q000517:prevention & control*; D010146:Pain / Q000188:drug therapy
D000701:Analgesics, Opioid; D000376:Agmatine; D009020:Morphine