[Methaemoglobin-behaviour due to carticaine (= Ultracain) (author's transl)]. / Methaemoglobinverhalten unter Anwendung von Carticain (= Ultracain).

The influence of carticaine on the formation of methaemoglobin was investigated in 22 patients undergoind spinal (n = 10) or epidural (n = 12) anaesthesia. Carticaine in a dose of 1,35 mg/kg, as used for spinal anaesthesia, did not influence the concentration of methaemoglobin. Carticaine in a dose of 5 mg/kg however, as used for epidural anaesthesia, increased the formation of methaemoglobin slightly at 30 min after injection. This increase is of little clinical importance since the upper limits of the normal range were not reached.

Phencyclidine and ketamine: comparison with the effect of cocaine on the noradrenergic neurones of the rat brain cortex.

In slices of rat occipital cortex, the influence of phencyclidine and ketamine on the accumulation of 3H-noradrenaline and the subsequent outflow of tritium was investigated, and was compared with the effect of cocaine.--All three drugs inhibited the accumulation of tritium during incubation of the slices with 3H-noradrenaline. Phencyclidine was slightly, whereas ketamine was much less effective than cocaine.--All three drugs accelerated the spontaneous outflow of tritium from slices preincubated with 3H-noradrenaline. The acceleration caused by low concentrations probably reflects an inhibition of the re-uptake of spontaneously released 3H-noradrenaline; in addition, high concentrations (10(-4) M phencyclidine, 3 X 10(-4)-10(-3) M cocaine and 10(-3)-3 X 10(-3) M ketamine) appear to release tritiated compounds from the neurones. The distance between uptake-inhibiting and releasing concentrations was much greater for cocaine than for phencyclidine and ketamine.--All three drugs enhanced the overflow of tritium evoked by electrical field stimulation. The increase probably reflects an inhibition of the re-uptake of released 3H-noradrenaline; in addition, phencyclidine appears to enhance the release of noradrenaline per pulse.--The actions of phencyclidine and ketamine on central noradrenergic neurones may contribute to the characteristic psychotropic side-effects of these general anaesthetics.

Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex.

By subcutaneous implantation of 2 or 13 morphine pellets (75 mg morphine/pellet), rats were made tolerant to, and dependent on narcotic analgesics. Occipital cortex slices from dependent animals and placebo-implanted controls were incubated with (-)-3H-noradrenaline and subsequently superfused with physiological salt solution. The accumulation of 3H-noradrenaline was not changed by pretreatment with 2, but was slightly decreased by pretreatment with 13 morphine pellets. The overflow of tritium evoked by electrical field stimulation was higher in slices from morphine-implanted rats than in those from placebo controls. Morphine and levorphanol, added in vitro, inhibited the stimulation-induced overflow of tritium at similar concentrations and to a similar degree in slices from morphineand placebo-pretreated animals.--It is concluded that, during chronic treatment with morphine, an adaptation takes place in the brain to compensate for the acute effect of narcotic analgesics, i.e. inhibition of the release of noradrenaline by nerve impulses. The chain of events from the drug-receptor interaction to the depression of the release process can be escluded as substrate of this adaptation. During withdrawal, the compensatory changes provoke an enhanced increase of extracellular noradrenaline during nerve impulses.

Influence of morphine and naloxone on the release of noradrenaline from rat cerebellar cortex slices.

In slices of rat cerebellar cortex preincubated with (-)-3H-noradrenaline, the influence of morphine and naloxone on the efflux of tritium was investigated. The spontaneous outflow was not changed by 10(-5) M of either morphine or naloxone. On the other hand, morphine caused a concentration-dependent decrease of the overflow of tritium evoked by electrical field stimulation. Naloxone did not change the stimulation-induced overflow, but prevented its inhibition by morphine. It is concluded that morphine, through an action on opiate receptors located on cerebellar noradrenergic neurones, inhibits the secretion of the transmitter in response to nerve impulses.

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.