A study on the ocular and extraocular pharmacology of metipranolol.
Metipranolol (Betamann) is a clinically efficacious ocular hypotensive drug and preclinical experiments were undertaken to characterize this beta-adrenoceptor antagonist. In vitro beta1- and beta2-adrenoceptor antagonism was evaluated using the guinea pig atrium and the rat uterus, respectively. The respective pA2 values were 8.3 and 8.4. Topical metipranolol, 0.3% and 0.6%, blocked both the hypotension (beta2-mediated) and the tachycardia (beta1-mediated) elicited in ganglion-blocked, conscious rabbits by isoproterenol, 0.5 microgram/kg, i.v. The Ki for displacement of 3H-dihydroalprenolol binding to rabbit iris + ciliary body homogenates was 34 nM. The effect of metipranolol, 0.3% and 0.6%, was not particularly striking on the intraocular pressure (IOP) of conscious, normotensive rabbits. However, the elevated IOP of the alpha-chymotrypsinized rabbit eye was significantly decreased (maximum reduction of 5.8 mm Hg) following the instillation of metipranolol, 0.3%. IOP recovery in conscious rabbits following hyperosmotic challenge (i.v. infusion of a 20% NaCl solution) was not decreased by a 1-h pretreatment with a 0.3% solution. In contrast, a significant reduction of 41% was elicited by a 0.6% solution. Hence, the ocular hypotensive effect of metipranolol may result from decreased aqueous humor inflow. Metipranolol, 0.6%, was devoid of effect on rabbit pupil diameter. However, corneal local anesthesia was elicited in the rabbit by both 0.3% and 0.6% solutions of the drug, the effect being more marked with the higher concentration.
Sugrue
M F
MF
Armstrong
J M
JM
Gautheron
P
P
Mallorga
P
P
Viader
M P
MP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002918:Chymotrypsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D014290:Metipranolol / Q000494:pharmacology*; D010812:Physical Stimulation; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D012965:Sodium Chloride; D002918:Chymotrypsin; D007545:Isoproterenol; D014290:Metipranolol