R. Botting, D. Burden
Jun 1, 1969
Citations
0
Influential Citations
1
Citations
Quality indicators
Journal
Journal of Pharmacy and Pharmacology
Abstract
The analeptic drug nikethamide is still used as a respiratory stimulant in intoxication with central depressants (Goodman & Gilman, 1965). We have observed that nikethamide does not antagonize the action of pentobarbitone in mice, but in fact significantly prolongs the pentobarbitone-induced sleeping time. Male mice (15-25 g) were injected with sodium pentobarbitone (45 mg/kg, i.p.). Sleeping time was measured as the time between loss and return of righting reflex. In a second group of animals, nikethamide (25 mg/kg) was injected intravenously 10 min after the barbiturate. Nikethamide significantly prolonged the sleeping time. There are two possible mechanisms for the potentiation of the action of sodium pentobarbitone by nikethamide. The analeptic or its metabolites could act as a depressant in mice, or nikethamide could inhibit the metabolism of the barbiturate. The former proposition does not seem likely since nikethamide produced no signs of depression when injected into mice of the same strain, rather it increased spontaneous movement. To test the second possibility, mice were pretreated with SKF 525A (diethylaminoethyl diphenylpropylacetate). This drug inhibits microsoma1 enzymes which metabolize barbiturate drugs (Brodie, 1956). Mice pretreated with 3 mg/kg SKF 525A slept five times longer than amimals given pentobarbitone alone. The dose of sodium pentobarbitone was reduced in order to induce a sleeping time approximately equivalent to that of the previous experiments. The results of this experiment are also recorded in Table 1. Nikethamide significantly reduced sleeping time when microsomal enzymes were inhibited. If a single dose of nikethamide was injected into normal mice 24 h before an experiment, sleeping time was shortened, this was presumably due to the known action of nikethamide in causing enzyme induction (Kato & Chiesara, 1962).