[Pharmacological characterization of the new highly potent beta-adrenergic receptor blocker soquinolol].
The present pharmacological test results characterize soquinolol (5-[3-tertiary butylamino-2-hydroxypropoxy]-2-formyl-1,2,3,4- tetrahydroisoquinoline mucate, We 704, Sertum) as a highly potent non-subtype-selective beta-adrenergic receptor blocker, which is devoid of any intrinsic sympathomimetic activity. Its localanaesthetic activity (membrane stabilizing effect) is very weak. It also shows good enteral efficacy and long duration of action. In binding studies with heart (Ki beta 1 = 3.25 nmol/l) and lung membranes (Ki beta 2 = 0.85 nmol/l) its binding profile was found to be similar to that of propranolol. Soquinolol inhibits the isoprenaline-induced tachycardia (EC50% = 48 micrograms/l) in the guinea-pig Langendorff heart in vitro to the same degree as propranolol. However, in the conscious dog soquinolol's beta 1-adrenergic blocking activity (ED 50%) on intravenous injection (5.5 micrograms/kg) and oral administration (5.8 micrograms/kg) is about twice as great as that of pindolol and 19 times (i.v.) or 138 times (p.o.) greater than that of propranolol. These results suggest 95% enteral efficacy for soquinolol (pindolol 88%, propranolol 13%). The differences in soquinolol's and propranolol's efficacy detected in vitro and in vivo are partially attributable to differences in their kinetic properties namely the lower protein binding and the higher distribution volume of soquinolol. In the conscious dog, soquinolol inhibits beta 1-(ED 50% = 4.0 micrograms/kg) and beta 2-receptors (ED 50% = 2.7 micrograms/kg) at dose levels which do not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Gries
J
J
Forschung und Entwicklung der Knoll AG, Ludwigshafen/Rhein.
Unger
L
L
Einig
H
H
Friedrich
L
L
Hofmann
H P
HP
Kreiskott
H
H
Lehmann
H D
HD
von Philipsborn
G
G
Wuppermann
D
D
Zimmermann
F
F
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013610:Tachycardia / Q000139:chemically induced; D044005:Tetrahydroisoquinolines
D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C058571:soquinolol; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol
Pharmakologische Charakterisierung des neuen, hochwirksamen beta-Rezeptorenblockers Soquinolol.