A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits.
BACKGROUND
Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine alpha-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, alpha-ergocryptine and ergocornine on the intraocular pressure and aqueous humor dynamics in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds.


METHODS
Experiments were conducted in albino ocular normotensive and hypertensive rabbits 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.


RESULTS
All natural ergot alkaloids tested reduced intraocular pressure in a dose-related fashion. The ocular hypotensive effect was greater in alpha-chymotrypsin-induced ocular hypertensive rabbits for the three compounds tested. All natural ergot alkaloids tested decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow in ocular normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits.


CONCLUSIONS
Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final effect in ocular normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits. Reductions in aqueous humor inflow observed after topical application of natural ergot alkaloids in alpha-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of aqueous humor, since processes involved in aqueous humor formation may probably be altered after alpha-chymotrypsin injection.
Puras
Gustavo
G
Department of Pharmacology, Universidad Autónoma de Tamaulipas, Tamaulipas, Mexico. gustavopuras@yahoo.es
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 / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage; D004876:Ergot Alkaloids / Q000008:administration & dosage*; D007429:Intraocular Pressure / Q000187:drug effects*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D014065:Tonometry, Ocular
D004873:Ergolines; D004876:Ergot Alkaloids; C100270:ergocristine; C100269:ergocryptine; C100271:ergocornine; D002918:Chymotrypsin; C117608:alpha-chymotrypsin