Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats.

The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.