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Cardiovascular effects of apraclonidine in the conscious dog
Author(s) -
Jones Carl E.,
Sallee Verney,
DeSantis Louis,
Gayheart Pamela A.,
Hamrick Melissa L.,
Bravenec J. Stanley,
Longlet Nancy A.
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280206
Subject(s) - dose , medicine , clonidine , heart rate , anesthesia , norepinephrine , blood pressure , mean arterial pressure , agonist , intraocular pressure , hemodynamics , endocrinology , surgery , dopamine , receptor
Apraclonidine (p‐aminoclonidine) a recognized α 2 ‐adrenergic agonist, has been approved for use with ocular laser surgery and is under consideration for use as a chronic treatment for glaucoma. The potential cardiovascular actions of apraclonidine in conscious animals has yet to be fully explored. The present studies were performed in conscious, chronically instrumented dogs to evaluate these possible cardiovascular effects. In a first study, apraclonidine was administered iv in dosages ranging from 5 to 200 μg. When administered by this route, apraclonidine elicited profound, but transient, cardiovascular actions. Mean arterial pressure (MAP) and left ventricular systolic pressure (LVSP) showed significant increases at dosages of 50–100 μg or higher, while heart rate (HR) showed a significant reduction. No variables had values significantly different from control values 60 min after administration. In a second study, apraclonidine was applied topically to either one or both eyes in total dosages of 125–1,000 μg. In contrast to iv administration, even with doses of up to 1,000 μg, topical apraclonidine administered in the eye elicited no significant change in cardiovascular variables. In the third set of studies, the neurotransmitters acetylcholine (1–10 μg/kg) and norepinephrine (0.2–2 μg/kg) were administered iv both before and 45 min after 500 μg apraclonidine was applied to the eye. Topical apraclonidine enhanced the mean AP response to norepinephrine by as much as 18% and the LVSP response to norepinephrine by as much as 17% No effect on the response to acetylcholine was seen. We conclude that all cardiovascular changes following iv apraclonidine can be attributed to its vasoconstrictor action with the consequent rise in MAP. The absence of measurable effects after topical application was likely due to a much slower entry into the circulation, although the vasoconstrictor action of apraclonidine after topical applications seemed to be additive to that of iv norepinephrine. © 1993 Wiley‐Liss, Inc.