Intraocular pressure lowering effects of the renin inhibitor ABBOTT-64662 diacetate in animals.
Corneal application of enalkiren (ABBOTT-64662), [N-(3-amino-3-methyl-1- oxobutyl)-4-methoxy-L-phenylalanyl]-N-[1S,2R,3S)-1-(cyclohexylmethyl+ ++)-2,3- dihydroxy-5-methylhexyl]-L-histidinamide], a renin inhibitor compound, lowered intraocular pressure (IOP) in unanesthetized rabbits and anesthetized monkeys. IOP was significantly decreased for at least 60 minutes after administration of a 0.3% solution of enalkiren in monkeys and for at least 90 minutes after the administration of 0.1% and 0.3% solutions in rabbits. Enalkiren did not affect systemic blood pressure or heart rate in anesthetized monkeys after topical application to the cornea. The IOP lowering activity of enalkiren suggests a potential functional role for the renin angiotensin system in the modulation of IOP.
Department of General Pharmacology, Abbott Laboratories, Abbott Park, IL.
W J
WJ
Giardina
H D
HD
Kleinert
D M
DM
Ebert
C T
CT
Wismer
M A
MA
Chekal
H H
HH
Stein
D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003315:Cornea; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D000092502:Renin Inhibitors
D004151:Dipeptides; D000092502:Renin Inhibitors; C056622:enalkiren