N-[2-hydroxy-5-[2-(methylamino)ethyl]phenyl]methanesulfonamide. A potent agonist which releases intracellular calcium by activation of alpha 1-adrenoceptors.
N-[2-Hydroxy-5-[2-(methylamino)ethyl]phenyl]methanesulfonamide (SK&F 102652) has been prepared and characterized pharmacologically. It is a potent agonist with an EC50 of 25 nM at alpha 1-adrenoceptors as determined in the isolated perfused rabbit ear artery. On the presynaptic alpha 2-adrenoceptors of the guinea pig atrium it was considerably weaker, demonstrating an EC50 for inhibition of neurotransmission of 1200 nM and thus an overall alpha 1/alpha 2 selectivity ratio of greater than or equal to 48. In the vascular smooth muscle of the canine saphenous vein an EC100 concentration of this agonist in the presence of zero external Ca2+ induced 37.9 +/- 1.4% of the maximal contractile response due to this agent while the endogenous ligand norepinephrine evoked only 14.5 +/- 0.4% of the maximum. In the presence of low (1 microM) external calcium, this agent produced 78.3 +/- 5.3% of maximum while norepinephrine gave 45.3 +/- 7.4%. This agent produces alpha 1-adrenoceptor-mediated contraction primarily by release of intracellular Ca2+ and should provide a useful tool for characterizing alpha 1-receptor subtypes.
DeMarinis
R M
RM
Lavanchy
P
P
Hieble
J P
JP
Jim
K F
KF
Matthews
W D
WD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D006168:Guinea Pigs; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; C044512:SK&F 102652; D002118:Calcium; D009638:Norepinephrine