PMID- 10781010
OWN - NLM
STAT- MEDLINE
DCOM- 20000627
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 130
IP  - 1
DP  - 2000 May
TI  - Activation of I(2)-imidazoline receptors enhances supraspinal morphine analgesia 
      in mice: a model to detect agonist and antagonist activities at these receptors.
PG  - 146-52
AB  - This work investigates the receptor acted upon by imidazoline compounds in the 
      modulation of morphine analgesia. The effects of highly selective imidazoline 
      ligands on the supraspinal antinociception induced by morphine in mice were 
      determined. 2. Intracerebroventricular (i.c.v.) or subcutaneous (s.c.) 
      administration of ligands selective for the I(2)-imidazoline receptor, 2-BFI, LSL 
      60101, LSL 61122 and aganodine, and the non selective ligand agmatine, increased 
      morphine antinociception in a dose-dependent manner. Neither moxonidine, a mixed 
      I(1)-imidazoline and alpha(2)-adrenoceptor agonist, RX821002, a potent 
      alpha(2)-adrenoceptor antagonist that displays low affinity at I(2)-imidazoline 
      receptors, nor the selective non-imidazoline alpha(2)-adrenoceptor antagonist 
      RS-15385-197, modified the analgesic responses to morphine. 3. Administration of 
      pertussis toxin (0.25 microg per mouse, i.c.v.) 6 days before the analgesic test 
      blocked the ability of the I(2)-imidazoline ligands to potentiate morphine 
      antinociception. 4. The increased effect of morphine induced by I(2)-imidazoline 
      ligands (agonists) was completely reversed by idazoxan and BU 224. Identical 
      results were obtained with IBI, which alkylates I(2)-imidazoline binding sites. 
      Thus, both agonist and antagonist properties of imidazoline ligands at the 
      I(2)-imidazoline receptors were observed. 5. Pre-treatment (30 min) with 
      deprenyl, an irreversible inhibitor of monoamine oxidase B (IMAO-B), produced an 
      increase of morphine antinociception. Clorgyline, an irreversible IMAO-A, given 
      30 min before morphine did not alter the effect of the opioid. At longer 
      intervals (24 h) a single dose of either clorgyline or deprenyl reduced the 
      density of I(2)-imidazoline receptors and prevented the I(2)-mediated 
      potentiation of morphine analgesia. 6. These results demonstrate functional 
      interaction between I(2)-imidazoline and opioid receptors. The involvement of 
      G(i)-G(o) transducer proteins in this modulatory effect is also suggested.
FAU - Sanchez-Blazquez, P
AU  - Sanchez-Blazquez P
AD  - Neuropharmacology, Institute of Neurobiology Santiago Ramon y Cajal, CSIC, 
      Madrid, Spain.
FAU - Boronat, M A
AU  - Boronat MA
FAU - Olmos, G
AU  - Olmos G
FAU - Garcia-Sevilla, J A
AU  - Garcia-Sevilla JA
FAU - Garzon, J
AU  - Garzon J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Analgesics)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Imidazoline Receptors)
RN  - 0 (Receptors, Drug)
RN  - 0 (Receptors, Opioid)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesia/methods
MH  - Analgesics/*pharmacology/therapeutic use
MH  - Analgesics, Opioid/*pharmacology/therapeutic use
MH  - Animals
MH  - Imidazoline Receptors
MH  - Male
MH  - Mice
MH  - Morphine/*pharmacology/therapeutic use
MH  - Pain/drug therapy/physiopathology
MH  - Receptors, Drug/*agonists/*antagonists & inhibitors/physiology
MH  - Receptors, Opioid/drug effects
PMC - PMC1572044
EDAT- 2000/04/26 09:00
MHDA- 2000/07/06 11:00
PMCR- 2001/05/01
CRDT- 2000/04/26 09:00
PHST- 2000/04/26 09:00 [pubmed]
PHST- 2000/07/06 11:00 [medline]
PHST- 2000/04/26 09:00 [entrez]
PHST- 2001/05/01 00:00 [pmc-release]
AID - 0703294 [pii]
AID - 10.1038/sj.bjp.0703294 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2000 May;130(1):146-52. doi: 10.1038/sj.bjp.0703294.