Alpha 1- and alpha 2-adrenoreceptor antagonists produce opposing mydriatic effects by a central action.
1. In anaesthetized rats, intravenous administration of alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) and raulwolscine (0.3-3.0 mg kg-1) produced a dose-related inhibition of sciatic nerve-(ScN) mediated reflex pupillary dilation (parasympatho-inhibition). The rank order of potency was idazoxan greater than yohimbine greater than rauwolscine. 2. Under similar experimental conditions, intravenous administration of alpha 1-adrenoreceptor antagonists prazosin (0.03-1.0 mg kg-1), phenoxybenzamine (0.3-3.0 mg kg-1) and corynanthine (0.03-1.0 mg kg-1) produced a dose-dependent potentiation of the reflex mydriasis with the potency order being prazosin greater than corynanthine greater than phenoxybenzamine. Intravenous yohimbine (1.5 mg kg-1) reversed the potentiation caused by the alpha 1-adrenoreceptor antagonists and blocked the reflex mydriasis. 3. Parasympatho-inhibition and mydriasis elicited by hypothalamic stimulation was not affected by the alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) or the alpha 1-adrenoreceptor antagonist prazosin (0.3-1.0 mg kg-1). 4. Microinjection of prazosin (3-30 ng) into the oculomotor nuclear complex (IIIn), produced a dose-related potentiation, whereas microinjection of yohimbine (0.3-3.0 micrograms) produced a dose-related blockade of reflex mydriasis. 5. The above findings support the hypothesis that ascending mechanisms (e.g. afferent ScN) produce inhibition of parasympathetic oculomotor tone to the iris by activation of central postsynaptic alpha 2-adrenoreceptors. Furthermore, these studies demonstrate that alpha 2-adrenoreceptor antagonists block and alpha 1-adrenoreceptor antagonists potentiate the reflex mydriasis. These actions appear to be localized within the pupilloconstrictor regions of the brain (oculomotor nuclear complex).
Hey
J A
JA
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
Koss
M C
MC
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008845:Microinjections; D009184:Mydriatics; D009802:Oculomotor Nerve / Q000187:drug effects / Q000502:physiology; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D009184:Mydriatics