The antinociceptive activities of 1-(4-aryl-2-thiazolyl)-3,5-disubstituted-2 pyrazolines in mouse writhing test.
OBJECTIVE
Sympathetic nervous system stimulation, which releases noradrenalin, influences the nociceptive activity that develops after tissue injury. The alpha2-adrenergic agonist, clonidine, produces analgesia through a central mechanism but also inhibits noradrenalin release at terminal nerve fiber endings.


METHODS
In this study the effects of some 1-(4-aryl-2-thiazolyl)-3,5-disubstituted-2-pyrazolines (compounds 1a-1e) as analogues of clonidine with some modifications were studied by writhing test, a visceral pain model in mice.


RESULTS
Compounds 1a and 1c induced significant reduction in writhing response when compared to control. Regarding the dose-response relationship of compounds 1a and 1c, it is evident that the activity of these compounds is in direct proportion to their dose and all compounds show activities comparable to clonidine. In addition compounds 1a and 1c, having methoxy and nitro groups respectively at para position of 4-aryl showed better antinociception than compounds having similar groups in meta position namely 1b and 1e. This might be due to better interaction of these compounds with the alpha2-receptors.


CONCLUSIONS
The antinociceptive properties of these newly synthesized compounds is comparable to clonidine. Further studies are needed to explore the differences in the efficacy and safety of synthesized compounds.
Shafiee
Abbas
A
Department of Medicinal Chemistry, Faculty of Pharmacy, and Laboratory of Chemistry, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Bagheri
Maryam
M
Shekarchi
Maryam
M
Abdollahi
Mohammad
M
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D011720:Pyrazoles; D003000:Clonidine; D009638:Norepinephrine