Comparative study of the analeptic-respirogenic agents doxapram HCl and nikethamide: II - respirogenic and cardiovascular pharmacodynamic activites in dogs

Experiments in pentobarbitone-sodium anesthetized dogs revealed that Doxapram HCl was a more potent respirogenic agent than Nikethamide; but at higher doses tachyphylaxis develops. Further assessments of its respirogenic activity in halothane-anesthetized dogs, by calculation of the minutevolume demonstrated a significant increase in ventilatic. These respirogenic effects were accompanied by transientrise in blood pressure at lower doses, and by bradycardia at higher doses. Nikethamide lowered the blood pressure at all dose levels, while it produced no ECG changes. Both drugs produced a dose-related direct myocardial depression of the isolated heart. The site of the respirogenic and cardiovascular effects of Doxapram HCl, was investigated after vagotomy, by intravertebral injection and in the spinal dog. The results demonstrated that the drug acts by central and peripheral mechnisms; and that its action may be partly through sympathetic influence

Effects of tranquillising, antidepressant and central nervous system stimulant drugs on the gamma-aminobutyric acid (GABA) level of rat brain.

The level of y-aminobutyric acid (GABA) was determined in the brain of rats 1 hr. after i.p. injection of chlorpromazine, prochlorperazine, diazepam, trimipramine, methamphetamine and nikethamide. Diazepam increased, and, trimipramine and amphetamine decreased the brain GABA level over wide dose ranges. Low doses of chlorpromazine and prochlorperazine increased but high doses of the drugs reduced the GABA level. Low doses of nikethamide reduced whereas high doses increased the level of GABA. The effects of the drugs have been discussed in relation to the brain GABA level.