Interaction between JWH133-induced Antinociception and two

Transkrypt

Interaction between JWH133-induced Antinociception and two
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żǀģŚƳŹŚǀƀŝƹƩƺưƘƯƽŚƷŻƹŵƹJWH133ŻřƪƇŚůƽŵŹŵƾŝźŧřƪųřŶţƾſŹźŝ
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Molecular
characterization
of
a
peripheral
1- Rodríguez de Fonseca F, Del Arco I,
receptor forcannabinoids. Nature.1993; 365: 61-5.
Bermudez-Silva FJ, Bilbao A, Cippitelli A,
8- Huffman JW, Liddle J, Yu S, et al. 3-(1',1'-
Navarro
system:
Dimethylbutyl)-1-deoxy-delta8-THC and related
physiology and pharmacology. Alcohol Alcohol.
compounds: synthesis of selective ligands for the
2005; 40: 2-14.
CB2 receptor. Bioorg Med Chem. 1999; 7:
2- Dogrul A, Gul H, Akar A, Yildiz O, Bilgin F,
2905-14.
Guzeldemir
cannabiniod
9- Dubuisson D, Dennis SG. The formalin test: a
antinociception: synergy with spinal sites. Pain.
quantitative study of the analgesic effects of
2003; 105: 11-6.
morphine, meperidine, and brain stem stimulation
3- Yesilyurt O, Dogrul A, Gul H, et al. Topical
in rats and cats. Pain. 1977; 4: 161-74.
cannabinoid
10- Tjølsen A, Berge OG, Hunskaar S, Rosland
M.
The
endocannabinoid
E.
Topical
enhances
topical
morphine
antinociception. Pain. 2003; 105: 303-8.
JH, Hole K. The formalin test: an evaluation of
4- Yeºilyurt O, Dogrul A. Lack of cross-tolerance
the method. Pain. 1992; 51: 5-17.
to
systemic
11- Hunter SA, Burstein S, Renzulli L. Effects of
and topical cannabinoids in morphine-tolerant
cannabinoids on the activities of mouse brain
mice.
lipases. Neurochem Res. 1986; 11: 1273-88.
the
antinociceptive
Neurosci
Lett.
effects
2004;
of
371:
122-7.
5- Dewey WL. Cannabinoid pharmacology.
12-
Pharmacol Rev. 1986; 38: 151-78.
mediation in cannabinoid stimulated arachidonic
6- Matsuda LA, Lolait SJ, Brownstein MJ, Young
acid mobilization and anandamide synthesis.
AC, Bonner TI. Structure of a cannabinoid
Life Sci. 1997; 60: 1563-73.
receptor and functional expression of the cloned
13- Khalilzadeh A, Tayebi Meybodi K, Vakili
cDNA.
Nature.
1990;
346:
561-4.
7- Munro S, Thomas KL, Abu-Shaar M.
Zarch
Hunter
A,
SA,
Burstein
Zarrindast
MR,
SH.
Receptor
Djahanguiri
B.
Discrepancy between effects of milligram and
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19
ƱřŹŚƨưƷƹƾƳŚƯźƸƣřźƷŻźŤƧŵ
nanogram doses of a COX-2 inhibitor (celecoxib)
model of neuropathic pain. Neuropharmacology.
on morphine state-dependent memory of passive
2006; 50: 814-23.
avoidance in mice. Brain Res Bull. 2005; 67:
21- Burstein S, Hunter SA. Prostaglandins and
443-7.
cannabis-VIII. Elevation of phospholipase activity
14- Dickenson AH, Sullivan AF. Peripheral
by cannabinoids in whole cells and subcellular
origins and central modulation of subcutaneous
preparations. J Clin Pharmacol. 1981; 21: 240-8S.
formalin-induced activity of rat dorsal horn
22-
neurons. Neurosci Lett. 1987; 83: 207-11.
Prostaglandins and cannabis. XII. The effect of
15- Ibrahim MM, Rude ML, Stagg NJ, et al. CB2
cannabinoid on the synthesis of prostaglandins by
cannabinoid
human lung fibroblast. Mol Pharmacol. 1983; 23:
receptor
mediation
of
Burstein
S,
Hunter
SA,
Ozman
K.
antinociception. Pain. 2006; 122: 36-42.
121-6.
16- Gühring H, Hamza M, Sergejeva M, et al. A
23-
role for endocannabinoids in indomethacin-
tetrahydrocannabinol
induced spinal antinociception. Eur J Pharmacol.
prostaglandins in the rat. Psychopharmacology.
2002; 454: 153-63.
1986; 90: 499-502.
17- Guindon J, De Léan A, Beaulieu P. Local
24-
interactions
prostaglandins
between
anandamide,
an
Bhattacharya
Laviolette
SK.
(THC)
M,
increases
Belanger
in
Delta9-
J.
brain
Role
of
marihuana-induced
endocannabinoid, and ibuprofen, a nonsteroidal
bronchodilation. Respiration. 1986; 49: 10-5.
anti-inflammatory
25- Hunter SA, Audette CA, Burstein S. Elevation
drug,
in
acute
and
inflammatory pain. Pain. 2006; 121: 85-93.
of brain prostaglandin E2 levels in rodents by
18- Yamaguchi T, Shoyama Y, Watanabe S,
delta-1-tetrahydrocannabinol.
Yamamoto T. Behavioral suppression induced by
Leukot Essent Fatty Acids. 1991; 43: 185-90.
cannabinoids
the
26- Shen KF, Crain SM. Ultra-low doses of
arachidonic acid cascade in rats. Brain Res. 2001;
naltrexone or etorphine increase morphine's
889: 149-54.
antinociceptive
19- Anikwue R, Huffman JW, Martin ZL, Welch
tolerance/dependence in mice. Brain Res. 1997;
SP. Decrease in efficacy and potency of
757: 176-90.
nonsteroidal anti-inflammatory drugs by chronic
27- Jonas W, Lin Y, Tortella F. Neuroprotection
delta(9)-tetrahydrocannabinol administration. J
from glutamate toxicity with ultra-low dose
Pharmacol Exp Ther. 2002; 303: 340-6.
glutamate.
20- Guindon J, Beaulieu P. Antihyperalgesic
28- Crain SM, Shen KF. Ultra-low concentrations
effects of local injections of anandamide,
of naloxone selectively antagonize excitatory
ibuprofen, rofecoxib and their combinations in a
effects of morphine on sensory neurons, thereby
is
due
to
activation
of
potency
Neuroreport.
Prostaglandins
and
2001;
attenuate
12:
335-9.
ÕÕƱŚŤƀŝŚţÓÔƽƵŹŚưƃ
ÎÔƽƵŹƹŵƱŚŬƳŻƾƳŚƯŹŵƾŤƃřŶƸŝšŚƯŶųƹƾƨƃżěƭƺƬƗƵŚĮƄƳřŵƾƄƷƹĦěƾưƬƗƽ
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JWH133ŻřƪƇŚůƽŵŹŵƾŝźŧřƪųřŶţƾſŹźŝ
increasing
and
action potential of mouse sensory ganglion
attenuating tolerance/dependence during chronic
neurons in dissociated cell cultures. Brain Res.
co-treatment. Proc Natl Acad Sci USA. 1995; 92:
1988; 462: 372-7.
10540-4.
32- Olive MF, Maidment NT. Opioid regulation
Downloaded from zums.ac.ir at 11:25 IRST on Wednesday March 8th 2017
29- Crain
its
SM,
antinociceptive
Shen
KF.
potency
20
Acute
thermal
of pallidal enkephalin release: bimodal effects of
hyperalgesia elicited by low- dose morphine in
locally administered mu and delta opioid agonists
normal mice is blocked by ultra-low dose
in freely moving rats. J Pharmacol Exp Ther.
naltrexone, unmasking potent opioid analgesia.
1998; 285: 1310-6.
Brain Res. 2001; 888: 75-82.
33- Raffa RB. Pharmacology of oral combination
30- Powell KJ, Abul-Husn NS, Jhamandas A,
analgesics: Rational therapy for pain. J Clin
Olmstead MC, Beninger RJ, Jhamandas K.
Pharm Ther. 2001; 26: 257-64.
Paradoxical effects of the opioid antagonist
34- Van Dyke T, Litkowski LJ, Kiersch TA,
naltrexone on morphine analgesia, tolerance, and
Zarringhalam NM, Zheng H, Newman K.
reward in rats. J Pharmacol Exp Ther. 2002; 300:
Combination oxycodone 5 mg/ibuprofen 400 mg
588-96.
for the treatment of postoperative pain: a double-
31- Chen GG, Chalazonitis A, Shen KF, Crain
blind, placebo- and active-controlled parallel-
SM. Inhibitor of cyclic AMP-dependent protein
group study. Clin Ther. 2004; 6: 2003-14.
kinase blocks opioid-induced prolongation of the
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ƱřŹŚƨưƷƹƾƳŚƯźƸƣřźƷŻźŤƧŵ
Interaction between JWH133-induced Antinociception and two extreme Doses of
Celecoxib
Ghahremani Z1, Rezaee-Kalaj S1, Zarrindast MR2, Djahanguiri B2, Jafari MR1
1
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Dept. of Physiology and Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
2
Dept. of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Corresponding Author: Jafari MR. Dept. of Physiology and Pharmacology, School of Medicine, Zanjan University of
Medical Sciences, Zanjan, Iran.
Email: [email protected]
Received: 31 Aug 2009
Accepted: 19 Sep 2009
Background and Objective: JWH133 is known to have cannabinoid-2 (CB2) receptor agonist properties.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is also known to have antinociceptive
properties. Endocannabinoids produce analgesia possibly through cyclooxygenase (COX) pathway. The aim
of the present work was: to study the effect of celecoxib on JWH133 induced antinociception and to
compare the effects of two different dose ranges of celecoxib (mg/kg and nano g/kg) on the JWH133
antiniciceptive effect.
Materials and Methods: We have studied the possible interaction of administration of mg/kg (50-200
mg/kg) and Ultra-Low Dose (ULD) (25 and 50 ng/kg) of celecoxib on the antinociceptive effect of
intraperitoneal (i.p.) injection of JWH133 using formalin test in mice.
Results: JWH133 (0.01, 0.1 and 1 mg/kg) induced antinociceptive effect just in phase I of the formalin test.
Celecoxib (50-200 mg/kg) and its ULD (25 and 50 ng/kg) attenuated and potentiated, JWH133 induced
antinociception, respectively.
Conclusions: It is concluded that JWH-133 induced antinociception is modulated by celecoxib and mg/kg
doses of celecoxib showed opposite effects compare to its ultra-low doses.
Key words: JWH133, Antinociception, Celecoxib, Ultra-Low Dose (ULD), Mice
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