Dexmedetomidine is a selective alpha 2-adrenoceptor agonist which has previously been shown to reduce the ocular pressure of normotensive rabbits as well as those with pressures artificially elevated by laser irradiation. In this study instillation of an equivalent hypotensive dose (12.5 micrograms) did not cause changes in heart rate, blood pressure, blood glucose or plasma catecholamine content even though dexmedetomidine could be detected in plasma. However, this dose given intravenously (i.v.) was also without effect. Higher ocular doses resulted in equivalent bradycardia and changes in blood glucose levels as when the dose was given i.v. These two parameters proved to be most sensitive indicators of systemic alpha 2-agonism, blood pressure did not change and plasma catecholamine levels were too low to be reliably assayed. It is concluded that when hypotensive doses of dexmedetomidine are instilled into the eye, intraocular concentrations are sufficiently high to exert pharmacological effects. As it is absorbed into the general circulation, it is diluted such that its systemic effects are minimal.
Dexmedetomidine i s a potent, specific, and selective a,-adrenoceptor agonist undergoing clinical trials as an adjunct to anesthesia. It may also have potential use in the treatment of glaucoma. In anesthetized rats and rabbits, dexmedetomidine induced marked bradycardia, rats being 5 times more sensitive than rabbits. In conscious rabbits, the bradycardia induced by dexmedetomidine was even less apparent; a dose of 40 pgkg was needed to consistently slow the pulse.Higher doses of dexmedetomidine induce a direct vasoconstrictor response in the anesthetized animals, in this case rabbits were 9 times less sensitive than rats. In both tests the anesthetized rat better mimicked the sensitivity of humans to dexmedetomidine. Thus, it should be remembered that in ocular pharmacology, where the rabbit i s the prevalent experimental animal used, this species i s relatively insensitive to the cardiovascular effects of this novel a,-adrenoceptor agOniSt. 0 1993 Wiley-Liss, Inc.
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