Porsius A J
Arch Int Pharmacodyn Ther. 1980 Dec;248(2):260-71.
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.
本研究的主题是开发一种经猫椎动脉给药的改良动物模型。已经证明，经左椎动脉注入药物（“经典”模型）主要积聚在延髓和脑桥的左侧。这种单侧、左侧分布与静脉给药后的分布不同，因为外周给药后两侧测量的药物浓度相等。此外，结果表明，静脉注射或经左椎动脉注入降压药异去甲槟榔碱丙酯（IAPE）达到同等降压剂量时，采用后一种给药途径会使脑桥下部的药物浓度高得多。这种差异归因于经左、右椎动脉给药时在脑桥延髓区域内的不对称分布模式。因此，通过左、右椎动脉同时注入药物。然后未观察到上述差异。此外，左右两侧的药物浓度处于相同数量级，且与静脉注射同等降压剂量后获得的浓度相当。与经左椎动脉给药相比，向椎动脉双侧注入可乐定、槟榔碱和IAPE会导致效力显著增加。总之，改良的椎动脉模型可被认为是测试药物对脑桥延髓区域可能的中枢作用的更合适方法。所呈现的给药技术在该脑区的药物浓度和相应的药理作用方面模仿了静脉注射途径。然而，给药剂量仅为静脉注射剂量的一小部分。
