Centrally induced cardiovascular effects and kinetic behaviour of isoarecaidine propyl ester in the cat
Porsius, A.J.; Lambrecht, G.; Moser, U.; Mutschler, E.
Archives Internationales de Pharmacodynamie et de Therapie 256(1): 22-35
1982
ISSN/ISBN: 0003-9780 PMID: 7092417 Document Number: 187193
Effects of isoarecaidine propyl ester (IAPE) on blood pressure and heart rate of the anesthetized cat were studied. The kinetic behavior of the drug in plasma and various brain tissues was also studied. The results indicate that the ester (4 mg/kg) induces a depressor effect and bradycardia after i.v. administration. IAPE injection (up to 60 .mu.g/kg) into the left vertebral artery lowers blood pressure in a dose-dependent manner. When administered simultaneously into the left and right vertebral artery, low doses (6 .mu.g/kg) produce a substantial fall in blood pressure. Although the fall in blood pressure after i.v. injection lasts for > 60 min, plasma half-life is extremely short (t1/2 = 6.3 s). The possible metabolism of the ester was studied in the pons, medulla oblongata and cerebellum. Thirty minutes after injection into the left vertebral artery, IAPE is almost entirely hydrolyzed in the pontomedullary region. This degradation is prevented by pretreatment with paraoxon, which abolishes the depressor action of IAPE. Evidently, accumulated isoarecaidine in the pontomedullary region is responsible for the depressor response to IAPE. Since IAPE does not seem to influence blood pressure and heart rate via a peripheral mechanism and lowers blood pressure and cardiac frequency by a central action, this drug is considered to be of pharmacological interest. The mechanism of action is discussed.