PMID- 17845912
OWN - NLM
STAT- MEDLINE
DCOM- 20080109
LR  - 20141120
IS  - 0361-9230 (Print)
IS  - 0361-9230 (Linking)
VI  - 74
IP  - 5
DP  - 2007 Oct 19
TI  - DAMGO and 6beta-glycine substituted 14-O-methyloxymorphone but not morphine show 
      peripheral, preemptive antinociception after systemic administration in a mouse 
      visceral pain model and high intrinsic efficacy in the isolated rat vas deferens.
PG  - 369-75
AB  - Peripheral micro-opioid receptors (MOR) have emerged as important components of 
      inhibitory nociceptive pathways. Here, the antinociceptive effects of MOR 
      agonists, the 6beta-glycine derivative of 14-O-methyloxymorphone (HS-731), DAMGO 
      and morphine were evaluated in a mouse model of visceral pain. The abdominal 
      acetic acid-induced writhing test was used to examine the peripheral, preemptive 
      antinociceptive opioid action on visceral nociception. HS-731 administered 
      subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dose-dependently and 
      completely inhibited writhing, being 24-598-fold more potent, depending on the 
      administration route, than two selective MOR agonists, the enkephalin analogue 
      [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO) and morphine. A longer 
      duration of action (2-3 h) was induced by HS-731 given before acetic acid, while 
      shorter effect was produced by morphine (30-60 min) and DAMGO (30-45 min). The 
      antinociceptive effects of systemic opioids were reversed by the s.c. opioid 
      antagonist, naloxone. Blocking of central MOR by the selective MOR antagonist 
      D-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP, i.c.v.) resulted in a 
      significant reduction of antinociception of s.c. morphine, whereas it completely 
      failed to antagonize the effects of systemic HS-731 or DAMGO. In in vitro 
      studies, HS-731 and DAMGO, but not morphine showed high intrinsic efficacy, 
      naltrexone-sensitive agonist effect at MOR of the rat vas deferens. These data 
      demonstrate that selective activation of peripheral MOR by systemic s.c. HS-731 
      or DAMGO produces potent peripheral, preemptive visceral antinociception, while 
      morphine's effects are mediated primarily through central mechanisms. Our 
      findings support the role of peripheral MOR in the pathology of pain states 
      involving sensitization of peripheral nociceptors.
FAU - Al-Khrasani, Mahmoud
AU  - Al-Khrasani M
AD  - Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 
      Hungary.
FAU - Spetea, Mariana
AU  - Spetea M
FAU - Friedmann, Tamas
AU  - Friedmann T
FAU - Riba, Pal
AU  - Riba P
FAU - Kiraly, Kornel
AU  - Kiraly K
FAU - Schmidhammer, Helmut
AU  - Schmidhammer H
FAU - Furst, Susanna
AU  - Furst S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070730
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 
      (2-((4,5alpha-epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino)acetic 
      acid)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (CTAP octapeptide)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Morphinans)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 51110-01-1 (Somatostatin)
RN  - 76I7G6D29C (Morphine)
RN  - Q40Q9N063P (Acetic Acid)
SB  - IM
MH  - Acetic Acid
MH  - Analgesics, Opioid/*administration & dosage
MH  - Animals
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Routes
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/*administration & dosage
MH  - Epoxy Compounds/*administration & dosage
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Morphinans/*administration & dosage
MH  - Morphine/*administration & dosage
MH  - Pain/chemically induced/*drug therapy
MH  - Pain Measurement
MH  - Peptide Fragments
MH  - Peptides/therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Somatostatin
MH  - Time Factors
MH  - Vas Deferens/*drug effects/physiology
EDAT- 2007/09/12 09:00
MHDA- 2008/01/10 09:00
CRDT- 2007/09/12 09:00
PHST- 2007/06/02 00:00 [received]
PHST- 2007/07/05 00:00 [revised]
PHST- 2007/07/05 00:00 [accepted]
PHST- 2007/09/12 09:00 [pubmed]
PHST- 2008/01/10 09:00 [medline]
PHST- 2007/09/12 09:00 [entrez]
AID - S0361-9230(07)00216-X [pii]
AID - 10.1016/j.brainresbull.2007.07.008 [doi]
PST - ppublish
SO  - Brain Res Bull. 2007 Oct 19;74(5):369-75. doi: 
      10.1016/j.brainresbull.2007.07.008. Epub 2007 Jul 30.