INVITRO INVESTIGATIONS OF BETA-AGONIST ACCUMULATION IN THE EYE

The eye is said to be the most accumulating tissue for beta2-adrenergic agonists in bovines. To avoid animal experiments, a perfusion system was developed for the eye. Therefore the eyes were perfused via arteria ophtalmica with defined amounts of Ringer solution containing 1 ng ml-1 of the respective beta-agonist [clenbuterol, mabuterol, 2-amino-3-chloro-5-(1'-hydroxy-2'-amino-tert-butylethyl)pyridine (ACP), salbutamol and terbutaline]. Beta-Agonists were extracted, cleaned-up with cartridges containing LiChrospher 60 RP select-B and determined by enzyme immunoassay. The tests prove accumulation for other beta-agonists also besides clenbuterol and the accumulation shows good correspondence to the metabolic stability in the organism [clenbuterol > mabuterol > 2-amino-3-chloro-5-(1'-hydroxy-2'-amino-tert-butyl-ethyl) pyridine > salbutamol > terbutaline]. The accumulation in retina + uvea was about 35 times higher than in vitreous humour + aqueous humour. The amount of accumulated clenbuterol corresponds with the volume of perfused Ringer solution containing the beta-agonist. Preliminary data investigating the visual system suggest a very weak, if any, interaction of beta-agonists with opsin.