alpha 2-Adrenoceptor agonists induced mydriasis in the rat by an action within the central nervous system.

Abstract

1 The effects of intravenous administration of the selective alpha 2-adrenoceptor agonists clonidine, UK 14,304 and guanoxabenz on rat pupil diameter were investigated. 2 In rats anaesthetized with pentobarbitone, each agonist produced a marked dose-related increase in pupil diameter; the rank order of potency was: clonidine greater than UK 14,304 greater than guanoxabenz. 3 Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 781094 (0.5 mg/kg, i.v.), produced a parallel 30-40 fold shift to the right of the dose-pupil dilator response curves for the three agonists. Yohimbine (1.5 mg/kg, i.v.) produced about a 10 fold rightward shift of the dose-response curve for guanoxabenz. In contrast, the alpha 1-selective antagonist, prazosin (0.5 mg/kg, i.v.), failed to affect the dose-response relation for guanoxabenz. 4 Several antagonists of varying selectivities towards alpha 1- and alpha 2-adrenoceptors were tested for their ability to reverse the maximal mydriasis induced by guanoxabenz (0.3 mg/kg, i.v.). The rank order of potency of the antagonists producing a 50% reversal of this effect was: RX 781094 greater than yohimbine greater than piperoxan = rauwolscine greater than mianserin greater than RS 21361. Neither corynanthine nor prazosin reversed the guanoxabenz-induced mydriasis. 5 Topical application of RX 781094 (0.1 to 3% w/v solutions) onto one eye produced a slow reversal of guanoxabenz-induced mydriasis; the time course and degree of reversal were virtually the same in both eyes. 6 Intracerebroventricular administration of RX 781094 (1.25-15 micrograms total dose) caused a rapid dose-related reversal of the maximal mydriasis induced by guanoxabenz (0.3 mg/kg, i.v.). 7 Guanoxabenz (0.3 and 1.0 mg/kg, i.v.) did not produce any dilation of the physostigmine-constricted undamaged pupil of the pithed rat. Intravenous adrenaline was found to produce a small mydriatic effect, while atropine completely antagonized the effects of physostigmine in this preparation. 8 These results indicate that alpha 2-adrenoceptor agonists induce mydriasis in the rat through a central alpha 2-adrenoceptor mechanism. However, the site of action within the central nervous system remains to be determined.

• Authors: T L Berridge, B Gadie, A G Roach, I F Tulloch
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 78 Issue 3 Pg. 507-15 (Mar 1983) ISSN: 0007-1188 [Print] England
• PMID: 6132641 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Dioxins
• Mydriatics
• Atropine
• Physostigmine
• Guanabenz
• guanoxabenz
• Idazoxan
• Epinephrine

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Atropine (pharmacology)
• Brain (drug effects)
• Dioxins (pharmacology)
• Epinephrine (pharmacology)
• Guanabenz (analogs & derivatives, pharmacology)
• Idazoxan
• Injections, Intraventricular
• Male
• Mydriatics
• Physostigmine (pharmacology)
• Pupil (drug effects)
• Rats
• Rats, Inbred Strains