PMID- 6162947
OWN - NLM
STAT- MEDLINE
DCOM- 19810526
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 213
IP  - 3
DP  - 1980 Jun
TI  - Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, 
      and antagonist, chlornaltrexamine.
PG  - 539-44
AB  - The 6-bis(2)chloroethyl)amino derivatives of oxymorphone and naltrexone, 
      chloroxymorphamine (COA) and chlornaltrexamine (CNA), respectively, produce an 
      irreversible inhibition of [3H]naltrexone binding to mouse brain homogenates. 
      Intracerebroventricular (i.c.v.) injection of COA (4 nmol/mouse) elicits 
      analgesia which lasts 4 times longer than analgesia produced by equimolar and 
      equieffective dose of oxymorphone. The analgesia induced by COA can be reversed 
      and blocked by naloxone. Injections of both COA and CNA i.c.v. antagonize 
      morphine-induced analgesia for 3 days. Similarly, when [3H]naltrexone binding is 
      measured in brains from mice pretreated i.c.v. with COA or CNA, there is a 
      significant decrease in total specific binding for 3 days after pretreatment. 
      These data suggest that CNA and COA alkylate the opioid receptors to produce 
      antagonist and agonist-antagonist effects, respectively. The implications of 
      these findings are discussed with respect to their effect on our perception of 
      the opioid receptor-narcotic agonist interaction and the mechanisms of tolerance 
      and dependence.
FAU - Caruso, T P
AU  - Caruso TP
FAU - Larson, D L
AU  - Larson DL
FAU - Portoghese, P S
AU  - Portoghese PS
FAU - Takemori, A E
AU  - Takemori AE
LA  - eng
GR  - DA 00289/DA/NIDA NIH HHS/United States
GR  - DA 01533/DA/NIDA NIH HHS/United States
GR  - GM01117/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Analgesics)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Narcotics)
RN  - 0 (Nitrogen Mustard Compounds)
RN  - 36B82AMQ7N (Naloxone)
RN  - 5S6W795CQM (Naltrexone)
RN  - 67025-94-9 (chlornaltrexamine)
RN  - 71360-45-7 (chloroxymorphamine)
RN  - 76I7G6D29C (Morphine)
RN  - 9VXA968E0C (Oxymorphone)
RN  - Q812464R06 (Hydromorphone)
SB  - IM
MH  - *Analgesics
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Hydromorphone/*analogs & derivatives
MH  - Male
MH  - Mice
MH  - Morphine/antagonists & inhibitors
MH  - Naloxone/*analogs & derivatives
MH  - Naltrexone/*analogs & derivatives/metabolism/pharmacology
MH  - Narcotic Antagonists/*pharmacology
MH  - Narcotics/*pharmacology
MH  - Nitrogen Mustard Compounds/*pharmacology
MH  - Oxymorphone/*analogs & derivatives/pharmacology
EDAT- 1980/06/01 00:00
MHDA- 1980/06/01 00:01
CRDT- 1980/06/01 00:00
PHST- 1980/06/01 00:00 [pubmed]
PHST- 1980/06/01 00:01 [medline]
PHST- 1980/06/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1980 Jun;213(3):539-44.