Effects of narcotic analgesics and their antagonists on the rabbit isolated heart and its adrenergic nerves.

1. In isolated perfused hearts of rabbits, the effects of morphine, methadone, pethidine, fentanyl, levallorphan and naloxone on heart rate, the spontaneous outflow of noradrenaline, the uptake of infused noradrenaline and the overflow of noradrenaline in response to stimulation of the accelerans nerves were investigated.2. At concentrations of 10-100 muM, methadone, fentanyl, levallorphan and naloxone, but not morphine and pethidine, decreased the heart rate. Only pethidine and levallorphan (100 muM) augmented the spontaneous outflow of noradrenaline.3. With the exception of naloxone, all drugs diminished the neuronal uptake of noradrenaline from the perfusion fluid. Methadone and pethidine (1 muM) were the most effective inhibitors. The inhibitory effect of morphine was not antagonized by naloxone.4. All drugs increased the overflow of noradrenaline evoked by stimulation of the accelerans nerves at 5 Hz. Simultaneously, the positive chronotropic effect of stimulation was usually enhanced. Morphine also augmented the response to stimulation at 2.5 and 10 Hz. The effect of morphine was prevented by pre-infusion of cocaine. The response to stimulation was never depressed.5. It is concluded that the adrenergic nerves of the rabbit heart lack specific morphine receptors which in some other sympathetic nerves mediate an inhibition of the stimulation-induced secretion of noradrenaline. The mechanism of the enhancement of adrenergic neurotransmission by relatively high concentrations of the drugs is discussed.