ACTIONS OF CHINOFORM AND OXINE ON THE ISOLATED PHRENIC NERVE-DIAPHRAGM PREPARATION OF THE RAT: THE ACCUMULATION OF CHINOFORM BY RAT DIAPHRAGM STRIP

The actions of chinoform and oxine on isolated phrenic nerve-diaphragm preparation of the rat and the uptake of chinoform by rat diaphragm strip were investigated. Chinoform and oxine decreased both twitch responses to indirect and, to a lesser extent, to direct stimuli in the rat phrenic nerve-diaphragm preparation. The depressant action of oxine was reversible whereas that of chinoform was irreversible and always accompanied by a marked rise in muscle tone. The neuromuscular block caused by these drugs was enhanced rather than antagonized by eserine and KCl. The depressant action and the rise in muscle tone caused by chinoform disappeared in vitro by lowering muscle temp., by suspending the drug in dog serum and also by conjugating it with glucuronic acid. When rat diaphragm strips were incubated aerobically in Krebs-bicarbonate solution containing chinoform for 1 to 5 hr at 37°C, the drug was accumulated against a concentration gradient until concentration ratio (muscle/medium) of up to 36: 1 had been attained. These findings indicate that rat diaphragm strips accumulate chinoform largely by intracellular binding and that the drug can act intracellularly as a metabolic poison.