The simultaneous infusion of drugs via the left and right vertebral artery of the cat; a modified animal model for the study of possible central actions of drugs upon the lower brain stem.

The development of a modified animal model for the administration of drugs via the vertebral arteries (v.a) of the cat is the subject of the present study. It has been demonstrated that drugs infused via the left v.a. (the "classical" model) accumulate mainly within the left part of the medulla oblongata and pons. This unilateral, leftsided distribution is different from that after intravenous application, since equal drug concentrations are measured at both sides after peripheral administration. Moreover, the results demonstrate that equihypotensive doses of the depressor agent isoarecaidine propyl ester (IAPE) infused either i.v. or via the left v.a. give rise to much higher drug concentrations in the lower brain stem when the latter route of administration is applied. This discrepancy is attributed to the unsymmetrical distribution pattern within the pontomedullary region when the drug is administered via the left and right v.a. Therefore drugs were simultaneously infused via the left and right v.a. Then the aforementioned discrepancy is not observed. Moreover, drug concentrations in the left and right sides are of the same order of magnitude and correspond with those obtained after the equihypotensive dose given i.v. Bilateral infusion of clonidine, arecoline and IAPE into the v.a. results in a significant increase in potency when compared with the administration via the left v.a. Conclusively, the modified vertebral artery model can be considered to be a more appropriate method to test possible central actions of drugs upon the pontomedullary region. The presented administration technique imitates the i.v. route with respect to drug concentrations in this brain region and the corresponding pharmacological effects. However, the dose to be administered is only a fraction of i.v. dose.