PMID- 15028575
OWN - NLM
STAT- MEDLINE
DCOM- 20040426
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1009
DP  - 2003 Dec
TI  - Spinal and supraspinal agmatine activate different receptors to enhance spinal 
      morphine antinociception.
PG  - 116-26
AB  - The endogenous clonidine-displacing substance, agmatine, enhances 
      morphine-induced antinociception and inhibits development of tolerance to 
      morphine. Because agmatine binds with relatively high affinity to both alpha(2) 
      adrenergic and imidazoline (I) receptors, the following studies were designed to 
      determine which receptor type is involved in the morphine-enhancing activity. 
      Mice were injected by various routes with agmatine, clonidine or norepinephrine 
      as well as selective antagonists, and tail flick antinociception was measured. 
      Agmatine administered subcutaneously (s.c.), intracerebroventricularly (i.c.v.), 
      or intrathecally (i.t.) had no antinociceptive activity, but enhanced the 
      antinociception produced by i.t. morphine. The morphine-enhancing activity of 
      i.c.v. agmatine (and clonidine) was attenuated by coadministered yohimbine, 
      idazoxan and SK and F 86466 (alpha(2) antagonists). When given i.t., agmatine, 
      yohimbine and SK and F 86466 attenuated the antinociception produced by 
      coadministered i.t. clonidine. In contrast, i.t. yohimbine and SK and F 86466, 
      but not agmatine, attenuated antinociception produced by i.t. norepinephrine. 
      These results suggested that agmatine actions were different at brain and spinal 
      sites. Thus, agmatine may act at both alpha(2) and I receptors in the brain and I 
      receptors in the spinal cord.
FAU - Roerig, Sandra C
AU  - Roerig SC
AD  - Department of Pharmacology and Therapeutics, LSU Health Sciences Center, 
      Shreveport, Louisiana 71130, USA. sroeri@lsuhse.edu
LA  - eng
GR  - DA07972/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Receptors, Adrenergic, alpha-2)
RN  - 70J407ZL5Q (Agmatine)
RN  - 76I7G6D29C (Morphine)
RN  - MN3L5RMN02 (Clonidine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic alpha-Agonists/pharmacology
MH  - Adrenergic alpha-Antagonists/pharmacology
MH  - Agmatine/administration & dosage/*metabolism/*pharmacology
MH  - Analgesics, Opioid/*pharmacology
MH  - Animals
MH  - Clonidine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Injections, Spinal
MH  - Male
MH  - Mice
MH  - Morphine/*pharmacology
MH  - Norepinephrine/pharmacology
MH  - Pain Measurement
MH  - Receptors, Adrenergic, alpha-2/metabolism
MH  - Spinal Cord/*drug effects/metabolism
EDAT- 2004/03/19 05:00
MHDA- 2004/04/27 05:00
CRDT- 2004/03/19 05:00
PHST- 2004/03/19 05:00 [pubmed]
PHST- 2004/04/27 05:00 [medline]
PHST- 2004/03/19 05:00 [entrez]
AID - 10.1196/annals.1304.011 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 Dec;1009:116-26. doi: 10.1196/annals.1304.011.