PMID- 11805202
OWN - NLM
STAT- MEDLINE
DCOM- 20020225
LR  - 20190607
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 300
IP  - 2
DP  - 2002 Feb
TI  - Dextromethorphan potentiates the antinociceptive effects of morphine and the 
      delta-opioid agonist SNC80 in squirrel monkeys.
PG  - 435-41
AB  - Dextromethorphan (DXM) is a noncompetitive N-methyl-D-aspartate (NMDA) receptor 
      antagonist shown to prevent the development of tolerance to the antinociceptive 
      effects of morphine in rodents. DXM also potentiates the antinociceptive effects 
      of the mu-opioid receptor agonist morphine under some conditions; however, the 
      effect of DXM in combination with opioids other than morphine has not been well 
      characterized. This study determined the antinociceptive effects of DXM 
      administered alone or in combination with morphine or the delta-opioid receptor 
      (DOR) agonist SNC80 using a squirrel monkey titration procedure. In this 
      procedure, shock (delivered to the tail) increases in intensity every 15 s 
      (0.01-2.0 mA) in 30 increments. Five lever presses during any given 15-s shock 
      period produces a 15-s shock-free period after which shock resumes at the next 
      lower intensity. This assay provides a measure of antinociception that is 
      separable from motor effects [response rate (RR)]. Morphine (0.3-3.0 mg/kg i.m.) 
      and SNC80 (1.0-10 mg/kg i.m.), but not DXM (1.0-10 mg/kg i.m.) dose- and 
      time-dependently increased the intensity below which monkeys (n = 4) maintained 
      shock 50% of the time [median shock level (MSL)]. Doses of morphine and SNC80 
      that alone did not increase MSL were potentiated by DXM. Importantly, these 
      combinations did not significantly alter RR. These data support previous findings 
      with other NMDA receptor antagonists and morphine using this procedure and also 
      extend those findings to a DOR agonist.
FAU - Allen, Richard M
AU  - Allen RM
AD  - Department of Psychology, University of North Carolina at Chapel Hill, 
      27599-3270, USA. ldystra@unc.edu
FAU - Granger, Arthur L
AU  - Granger AL
FAU - Dykstra, Linda A
AU  - Dykstra LA
LA  - eng
GR  - DA00033/DA/NIDA NIH HHS/United States
GR  - R37-DA02749/DA/NIDA 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, Opioid)
RN  - 0 (Antitussive Agents)
RN  - 0 (Benzamides)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Isoquinolines)
RN  - 0 (Piperazines)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Opioid, delta)
RN  - 156727-74-1 
      (4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - 76I7G6D29C (Morphine)
RN  - AR2BHC0C6P (LY 235959)
RN  - F2JLV9220T (1-hydroxy-3-amino-2-pyrrolidone)
SB  - IM
MH  - Analgesics, Opioid/*pharmacology
MH  - Animals
MH  - Antitussive Agents/*pharmacology
MH  - Benzamides/*pharmacology
MH  - Conditioning, Operant/drug effects
MH  - Dextromethorphan/*pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Drug Synergism
MH  - Electroshock
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Isoquinolines/pharmacology
MH  - Male
MH  - Morphine/*pharmacology
MH  - Pain Measurement/drug effects
MH  - Piperazines/*pharmacology
MH  - Pyrrolidinones/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Receptors, Opioid, delta/*agonists
MH  - Saimiri
EDAT- 2002/01/24 10:00
MHDA- 2002/02/28 10:01
CRDT- 2002/01/24 10:00
PHST- 2002/01/24 10:00 [pubmed]
PHST- 2002/02/28 10:01 [medline]
PHST- 2002/01/24 10:00 [entrez]
AID - 10.1124/jpet.300.2.435 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Feb;300(2):435-41. doi: 10.1124/jpet.300.2.435.