Cardiovascular and ventilator effects of vadocaine hydrochloride in urethane-anaesthetized rats and guinea-pigs.
Urethane-anaesthetized rats and guinea-pigs were used to compare the cardiovascular, electrocardiac and ventilator effects of Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine), lidocaine hydrochloride and codeine phosphate. In rats, vadocaine and lidocaine, only at the largest dose tested (64 mumol/kg i.v.), reduced mean arterial pressure (MAP), heart rate (HR) and ventilation rate (VR). Codeine reduced VR dose-dependently, MAP decreased only at the largest dose of 64 mumol/kg, and HR was not affected at the doses tested. In guinea-pigs, neither vadocaine nor lidocaine had any clear effects on MAP. HR was significantly reduced at the doses of 4 and 16 mumol/kg of vadocaine and 16 and 64 mumol/kg of lidocaine. Vadocaine and lidocaine 16 mumol/kg i.v. caused a significant reduction in VR. Lidocaine 64 mumol/kg did not further reduce VR. The electrocardiac effects included prolongation of P-Q interval both in the vadocaine and lidocaine group. Prolongation of Q-Tc, deepening of Q and S, decrease in R amplitude, and inversion of T waves were seen only in the vadocaine group. To induce changes in the P-Q interval, four times less vadocaine than lidocaine was needed. The acute toxic dose of vadocaine in rats ranged from 64 to 100 mumol/kg i.v.; lidocaine and codeine caused no lethalities in rats at the dose range 1-64 mumol/kg i.v. In guinea-pigs, the lethal dose of 64 mumol/kg i.v. produced AV blocks followed by asystole or ventricular fibrillation. At the dose of 64 mumol/kg i.v. of lidocaine 3 guinea-pigs out of 11 died.
Paakkari
I
I
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Svartström-Fraser
M
M
D000758:Anesthesia; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D014520:Urethane
D000996:Antitussive Agents; D010880:Piperidines; D014520:Urethane; C051410:vadocaine