Mechanism of dexamphetamine-induced mydriasis in the anaesthetized rat.
1. The effect of intravenous administration of dexamphetamine [+)-Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. 2. In rats anaesthetized with urethane, (+)-Amp (0.1-0.3 mg kg-1, i.v.) produced a dose-related increase in pupil size. The mydriatic effects of (+)-Amp were evident immediately after administration. 3. Pretreatment with the alpha 2-adrenoceptor antagonists yohimbine (1.5 mg kg-1 i.v.) or idazoxan (0.5 mg kg-1, i.v.) blocked the pupillary response to (+)-Amp. Yohimbine caused about a 30 fold shift to the right in the dose-response curve whereas idazoxan almost completely abolished the mydriatic response to (+)-Amp. 4. In contrast, pretreatment with the alpha 1-adrenoceptor antagonist phenoxybenzamine (2 mg kg-1, i.v.), failed to alter significantly the pupillary response to (+)-Amp. 5. Depletion of central nervous system (CNS) monoamines with reserpine (5 mg kg-1, i.p.) and alpha-methyl-p-tyrosine (2 x 300 mg kg-1, i.p.) prevented the pupillary response to (+)-Amp. 6. The mydriatic effect of (+)-Amp was present only in preparations that had intact parasympathetic neural tone to the iris. Central preganglionic denervation of the oculomotor nerve abolished the mydriatic response of (+)-Amp. 7. These results indicate the (+)-Amp acts in the CNS to produce mydriasis in the anaesthetized rat by stimulating CNS postsynaptic alpha 2-adrenoceptors, findings that are consistent with the hypothesis that (+)-Amp acts predominantly as an indirect sympathomimetic agent to release endogenous stores of a monoaminergic neurotransmitter (perhaps noradrenaline).
Hey
J A
JA
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Ito
T
T
Koss
M C
MC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology; D003714:Denervation; D003913:Dextroamphetamine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D019329:Idazoxan; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009802:Oculomotor Nerve / Q000502:physiology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D014520:Urethane / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D000317:Adrenergic alpha-Antagonists; D015306:Biogenic Monoamines; D004146:Dioxanes; D008781:Methyltyrosines; D010643:Phenoxybenzamine; D015016:Yohimbine; D014520:Urethane; D019805:alpha-Methyltyrosine; D012110:Reserpine; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine; D019329:Idazoxan