No abstract

Experiments were carried out in mice to assess the protection provided by thiopentone (Intraval, May and Baker) and propofol (Diprivan, I.C.I.) against epileptiform seizures induced by electroshock and pentylenetetrazol. Intraperitoneal administration of propofol 50 mg kg-1 and thiopentone 25 mg kg-1 produced similar peak behavioural effects of mild sedation and incoordination. However, at these doses propofol afforded a greater degree of protection against pentylenetetrazol than thiopentone and at greater doses both propofol and thiopentone caused marked protection. Both anaesthetics were effective also against electroshock seizures at sedative doses. We conclude that propofol has strong anticonvulsant properties.

Intrathecal midazolam causes antinociception by combining with spinal cord benzodiazepine receptors. This effect is reversible with doses of naloxone, suggesting involvement of spinal kappa or delta but not mu opioid receptors. The antinociceptive effects of intrathecally administered drugs in the spinal cord were demonstrated by measurements of the electrical current threshold for avoidance behaviour in rats with chronically implanted lumbar intrathecal catheters. A comparison was made of suppression by two opioid selective antagonists (nor-binaltorphimine (kappa selective) and naltrindole (delta selective)) of spinal antinociception caused by equipotent doses of opioids selective for different receptor subtypes (U-50488H (kappa), DSLET and DSBULET (delta), fentanyl (mu)) and the benzodiazepine midazolam. Nor-binaltorphimine selectively suppressed the effects of U-50488H but not midazolam or fentanyl. However, the delta selective antagonist, naltrindole, caused dose-related suppression of antinociception produced by both delta opioid agonists and midazolam with the same ED50 (0.5 nmol). We conclude that intrathecal midazolam caused spinally mediated antinociception in rats by a mechanism involving delta opioid receptor activation.

Isolated hepatic portal veins and aorta taken from the rat were used to investigate the direct action of the intravenous anaesthetic propofol. This compound is known to produce a fall in blood pressure in man and animals and it has been suggested that the hypotension may result from a direct vasodilator action on the veins and arterioles. In our experiments propofol caused a dose related decrease of potassium-induced tone in both types of blood vessel. However, the concentrations required to produce this effect in the experiments on veins were significantly lower than those required to produce similar changes in the isolated artery preparation. We conclude that this direct action may contribute towards the hypotensive effects of propofol.

Two methods are described for determination of octanoic and decanoic acids in plasma and brain homogenate by "high-performance" liquid chromatography with ultraviolet detection. Analysis of the underivatized acids had a detection limit of only 50 mg/L, but formation of the p-bromophenacyl ester increased the sensitivity by 100-fold, to a detection limit of 0.5 mg/L. The latter procedure gave interassay coefficients of variation of 4.1% and 4.8% for octanoic and decanoic acids, respectively. The corresponding intra-assay values were 3.95% and 4.7% (n = 6). The derivative method, applied to samples of plasma from children receiving a medium-chain triglyceride (MCT) diet, gave values in agreement with results by gas-liquid chromatography. Results have also been obtained for samples from mice, either treated with the medium-chain triglyceride diet or given infusions of sodium octanoate.