A pyrazolyl-thiazole derivative causes antinociception in mice.
The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 micromol/kg, s.c.) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 +/- 6.15; B50 (8 micromol/kg): 16.92 +/- 3.84; B50 (23 micromol/kg): 13.85 +/- 3.84; B50 (80 micromol/kg): 9.54 +/- 3.08; data are reported as means +/- SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 micromol/kg, s.c.) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 +/- 3.15; vehicle-naloxone: 27.41 +/- 3.70; B50 (80 micromol/kg)-saline: 8.70 +/- 3.33; B50 (80 micromol/kg)-naloxone: 31.84 +/- 4.26; morphine-saline: 2.04 +/- 3.52; morphine-naloxone: 21.11 +/- 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test.
Prokopp
C R
CR
Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Setor de Bioquímica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brasil.
Rubin
M A
MA
Sauzem
P D
PD
de Souza
A H
AH
Berlese
D B
DB
Lourega
R V
RV
Muniz
M N
MN
Bonacorso
H G
HG
Zanatta
N
N
Martins
M A P
MA
Mello
C F
CF
D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011930:Reaction Time; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
C518623:2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole; D000700:Analgesics; D009292:Narcotic Antagonists; D011720:Pyrazoles; D013844:Thiazoles; D009270:Naloxone; D019342:Acetic Acid