Modulation of opioid analgesia by agmatine Journal Article
| Authors: | Kolesnikov, Y.; Jain, S.; Pasternak, G. W. |
| Article Title: | Modulation of opioid analgesia by agmatine |
| Abstract: | Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. δ-Opioid receptor-mediated analgesia also is potentiated by agmatine, but κ1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl] benzeneacetemide) and κ3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the δ-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the κ3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on κ1-opioid analgesia in the acute model, agmatine prevents κ1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance. |
| Keywords: | controlled study; unclassified drug; drug potentiation; nonhuman; mouse; animal model; morphine; analgesia; morphine tolerance; tail flick test; tolerance; opiate receptor; enkephalin[2,5 dextro penicillamine]; gastrointestinal transit; yohimbine; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone; intraperitoneal drug administration; subcutaneous drug administration; intracerebroventricular drug administration; male; priority journal; article; delta opiate receptor agonist; intrathecal drug administration; agmatine; idazoxan; kappa 1 opiate receptor agonist; kappa 3 opiate receptor agonist |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 296 |
| Issue: | 1 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 1996-01-18 |
| Start Page: | 17 |
| End Page: | 22 |
| Language: | English |
| DOI: | 10.1016/0014-2999(95)00669-9 |
| PUBMED: | 8720472 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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414Pasternak -
23
Jain
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