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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Evaluation of the alpha 1- and alpha 2-adrenoceptor effects of detomidine, a novel veterinary sedative analgesic.

The in vitro receptor interactions of detomidine, a novel veterinary sedative analgesic, were studied. Detomidine caused a concentration-dependent inhibition of the twitch response in electrically stimulated mouse vas deferens with a pD2 value of 8. 8. Clonidine and xylazine had the same effect with pD2 values of 8.7 and 7.5, respectively. The effect of detomidine was competitively antagonized by the alpha 2-blocking agents yohimbine, rauwolscine and idazoxan but not by the alpha 1-antagonists prazosin and corynanthine. The effect of detomidine was not antagonized by the opioidergic antagonist naloxone, the dopaminergic antagonist sulpiride, the serotonergic antagonist methysergide, the histamine H2-antagonist cimetidine, the histamine H1-antagonist diphenhydramine and the cholinergic muscarine antagonist atropine. Detomidine, as well as clonidine and xylazine, produced concentration-dependent contractions of rat anococcygeal muscle and rabbit aortic strips with pD2 values between 2.5 and 6. 4. Intrinsic activities (compared to phenylephrine) varied between 0.5 and 0. 7. The effects of detomidine in these two muscles could be antagonized by low concentrations of prazosin. In receptor binding experiments detomidine showed strong affinity to alpha 2-receptors. There was some binding affinity towards alpha 1-receptors also but only negligible or no affinity towards dopamine, opiate and adenosine receptors. In conclusion, the present results suggest that detomidine is a potent alpha 2-adrenoceptor agonist and that at high concentrations it can also stimulate alpha 1-adrenoceptors.[1]

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