Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 324, Issue 3, pp 201–206 | Cite as

Alpha-methyl-DOPA induced mydriasis in the cat

Relationship between pupillary response and the oculomotor perfusate concentration of methyldopa and its metabolites
  • Tseggai Gherezghiher
  • Michael C. Koss
  • H. Dix Christensen
Article

Summary

In pentobarbital anaesthetized cats, intravenous administration of 30 mg/kg, alpha-methyl-DOPA produced mydriasis that reached a maximum plateau in 2–2.5 h. The oculomotor nucleus was perfused with saline using a pushpull cannula system chronically implanted over the nucleus. Perfusate samples were collected and subsequently analyzed by liquid chromatography with electrochemical detection (LC-EC). Alpha-methyl-DOPA administration resulted in a gradual build up of alpha-methyl-noradrenaline to approximately 32 μmoles over the 3 h sampling period. In contrast, the concentration of alpha-methyl-dopamine was below the detection level for the first 90 min with peak leves of less than 6 μmoles after 3 h. A linear regression analysis demonstrated a negative correlation (R=0.90) between the pupil size and the perfusate concentration of alpha-methyl-DOPA and a positive correlation for both alpha-methyl-dopamine and alpha-methyl-noradrenaline (R=0.88 and 0.94 respectively). Pretreatment with the DOPA-decarboxylase inhibitor, 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg/kg, i.p.) completely blocked the mydriatic response to alpha-methyl-DOPA, with neither alpha-methyl-dopamine nor alpha-methyl-noradrenaline reaching detectable levels in the oculomotor perfusate. After pretreatment with the dopamine-beta-hydroxylase inhibitor, bis (4-methyl-homopiperazinyl thiocarbonyl) disulfide (FLA-63; 2.5 mg/kg, i.p.) there was a significant accumulation of alpha-methyl-dopamine when compared to that obtained in the alpha-methyl-DOPA controls but with no apparent alpha-methyl-dopamine related pupillary dilation. However, the correlation between alpha-methyl-noradrenaline concentration and the increase in the diameter of the pupil was maintained. The results of the pupillary response-neurochemical correlation studies conclusively show that pupillary responses to alpha-methyl-DOPA administration are not correlated with alterations of endogenous amine concentration, nor to the CNS levels of alpha-methyl-DOPA or alpha-methyl-dopamine. There is however, a very high and consistent correlation between alpha-methyl-noradrenaline oculomotor nucleus perfusate concentration and pupil size. As the correlation was maintained after three different doses of alpha-methyl-DOPA as well as after the administration of selective blockers of the enzymes involved in catecholamine biosynthesis, these results suggest that alpha-methyl-noradrenaline is the active metabolite responsible for the mydriatic effect of alpha-methyl-DOPA in the cat.

Key words

Alpha-methyl-DOPA Alpha-methyl-dopamine Alpha-methyl-noradrenaline Oculomotor perfusate amine concentration Pupillary diameter 

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Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Tseggai Gherezghiher
    • 1
    • 2
  • Michael C. Koss
    • 1
    • 2
  • H. Dix Christensen
    • 1
    • 2
  1. 1.Departments of Pharmacology and of OphthalmologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Dean McGree Eye InstituteOklahoma CityUSA

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