N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine.
N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1) is a novel alpha(1) agent having the unique profile of alpha(1A) (rabbit urethra, EC(50) = 0.60 microM) agonism with alpha(1B) (rat spleen, pA(2) = 5.4) and alpha(1D) (rat aorta, pA(2) = 6.2) antagonism. An in vivo dog model showed 1 to be more selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the active metabolite of midodrine), and phenylpropanolamine (4).
Altenbach
Robert J
RJ
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA. Robert.j.altenbach@abbott.com
Khilevich
Albert
A
Meyer
Michael D
MD
Buckner
Steven A
SA
Milicic
Ivan
I
Daza
Anthony V
AV
Brune
Michael E
ME
O'Neill
Alyssa B
AB
Gauvin
Donna M
DM
Cain
John C
JC
Nakane
Masaki
M
Holladay
Mark W
MW
Williams
Michael
M
Brioni
Jorge D
JD
Sullivan
James P
JP
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008879:Midodrine / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000502:physiology
C466636:ABT 866; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D010665:Phenylpropanolamine; D008879:Midodrine