Alpha-methyl-DOPA induced mydriasis in the cat. Relationship between pupillary response and the oculomotor perfusate concentration of methyldopa and its metabolites.
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 push-pull 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 mumoles 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 levels of less than 6 mumoles 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-decarboxylate 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 treatment 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001679:Biogenic Amines / Q000032:analysis; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002415:Cats; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008750:Methyldopa / Q000378:metabolism / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects*
D001679:Biogenic Amines; D006834:Hydrazines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D008750:Methyldopa; C004297:3-hydroxybenzylhydrazine