The effect of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in rabbits with alpha-chymotrypsin-induced ocular hypertension.
BACKGROUND
We previously reported that topical natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive rabbits, most likely by decreasing aqueous humor inflow. In the present study, the effects of these compounds on intraocular pressure and aqueous humor dynamics in a rabbit model for ocular hypertension were assessed.


METHODS
Experiments were conducted in albino rabbits made ocular hypertensive by intracameral injection of alpha-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined in order to obtain dose-response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on aqueous humor dynamics in alpha-chymotrypsin-induced ocular hypertensive rabbits.


RESULTS
Topical application of the natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine lowered intraocular pressure in alpha-chymotrypsin-induced ocular hypertensive rabbits in a dose-related fashion, with ergocristine displaying the greatest intraocular pressure-lowering effect. Tonographic studies revealed a decrease in the tonographic outflow facility following topical application of natural ergot alkaloids, although only the effects of both ergocristine and alpha-ergocryptine reached statistical significance. All natural ergot alkaloids tested significantly reduced the calculated aqueous humor inflow.


CONCLUSIONS
This study suggests that the natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine effectively decrease intraocular pressure in the alpha-chymotrypsin-induced model of ocular hypertension. Since these compounds reduce the tonographic aqueous humor outflow facility, their final ocular antihypertensive effect appears to result from a remarkable reduction of the aqueous humor inflow.
Puras
Gustavo
G
Department of Pharmacology, Faculty of Pharmacy, Universidad del País Vasco, Paseo de la Universidad 7, 01006 Vitoria, Spain.
Santafé
Juan
J
Segarra
José
J
Garrido
Manuel
M
Melena
José
J
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D002918:Chymotrypsin; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage / Q000627:therapeutic use*; D007429:Intraocular Pressure / Q000187:drug effects*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009883:Ophthalmic Solutions; D011817:Rabbits; D014065:Tonometry, Ocular
D004873:Ergolines; D009883:Ophthalmic Solutions; C100270:ergocristine; C100269:ergocryptine; C100271:ergocornine; D002918:Chymotrypsin; C117608:alpha-chymotrypsin