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Biomedical subjects

S H Ngai

Publications and source records attributed to S H Ngai.

At least 19 recordsLinked to original sources
PubMed1988

Morphine tolerance decreases the analgesic effects of ketamine in mice.

Previous studies have shown that ketamine interacts with opiate receptors, and it has been suggested that ketamine-induced analgesia is mediated through opiate receptors. If so, ketamine should produce less analgesia in morphine tolerant animals, just as morphine does. To test this hypothesis, the analgesic effects of ketamine were tested in mice implanted with placebo pellets and in mice made tolerant to morphine through implantation of morphine pellets, using the abdominal constriction test. The test consisted of ip injection of 1% acetic acid, which caused stretching of hind limbs and constriction of abdominal muscles, also called writing. The number of writhes was counted for each mouse 10-15 min following acetic acid injection. Morphine pellet implanted mice treated with saline writhed 12.2 +/- 0.8 times (mean +/- SEM), not significantly different from 9.8 +/- 0.9 times seen in placebo pellet implanted mice. Treatment of the animals with ketamine at three doses of 20, 25, and 30 mg/kg, subcutaneously (sc), reduced the number of writhes in the placebo pellet implanted group to 5.8 +/- 0.8, 4.2 +/- 0.7, and 1.3 +/- 0.3, respectively. In the morphine pellet-implanted group, with the same doses of ketamine, the numbers of writhes were 10 +/- 0.9, 9.3 +/- 1.1, and 5.2 +/- 0.9, respectively. Morphine-tolerant animals writhed significantly more at each dose of ketamine, indicating that they were cross tolerant to the analgesic effects of ketamine.

Analgesia↗
PubMed1979

Tolerance to nitrous oxide analgesia in rats and mice.

The purpose of these experiments was to characterize the nature of tolerance to the analgesic action of nitrous oxide. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to nitrous oxide, 75 per cent, the balance oxygen, continuously for 16--18 hours. On re-exposure to nitrous oxide 30 min later, these animals were found tolerant to nitrous oxide in that the analgesic response was decreased by at least 50 per cent. Animals tolerant to nitrous oxide were not tolerant to morphine. Morphine (0.25--1.5 mg/kg) produced equal degrees of analgesia in control and nitrous oxide-tolerant mice and rats. In contrast, rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg subcutaneously or by subcutaneous implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to nitrous oxide. Thus the cross-tolerance between nitrous oxide and morphine appears unique in that it is unidirectional.

Anesthesia, General↗
PubMed1978

Acetylcholine concentrations and turnover in rat brain structures during anesthesia with halothane, enflurane, and ketamine.

Acetylcholine and choline concentrations in brain structures of rats during anesthesia with halothane (0.7-1.0 per cent inspired), enflurane (2.7-3.0 per cent, inspired) and ketamine (40 mg/kg, iv) were measured by gas chromatography. The turnover rate (biosynthesis) of acetylcholine in vivo was estimated by infusing phosphoryl(Me-14C)choline intravenously, determining specific activities of choline and acetylcholine, and applying principles of steady-state kinetics to compute the fractional rate constant of acetylcholine. Acetylcholine concentrations in brain structures did not change during anesthesia. Halothane decreased the acetylcholine turnover rates in all parts of the brain. Enflurane decreased the acetylcholine turnover rate in the cerebral cortex only, but not in the caudate nucleus, the hippocampus, and the hypothalamic and thalamic regions. During anesthesia with ketamine, acetylcholine turnover rates were reduced in the caudate nucleus and the hippocampus, but not in the cerebral cortex and the hypothalamic and thalamic regions. The results suggest that acetylcholine turnover rate and utilization are related to anesthetic induced electrophysiologic changes in cortical and subcortical structures.

Acetylcholine↗
PubMed1977

Antagonism of general anesthesia by naloxone in the rat.

The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system.

Anesthesia, General↗
PubMed1977

Nitrous oxide analgesia: reversal by naloxone and development of tolerance.

The objective of this study was to characterize further the nature of nitrous oxide analgesia and to establish if tolerance to nitrous oxide occurs. Methods for studying the analgesic action of a gas are described. In mice, nitrous oxide is analgesic in the phenylquinone and acetic acid abdominal constriction tests. Aspirin and very high doses of alcohol are also active in these tests; however, only nitrous oxide-induced analgesia is antagonized by narcotic antagonists. These data indicate the mechanism of action of nitrous oxide analgesia differs from that of the other two drugs. Nitrous oxide produced a dose-related analgesic response in rats (ED50, 67%) as measured by the tail-flick method. Naloxone, 5 to 30 mg/kg, also antagonized nitrous oxide analgesia in rats. Lower doses of the antagonist were not effective. Tolerance developed to the effects of nitrous oxide in both rats and mice after prolonged exposure. These data lend support to the hypothesis that nitrous oxide and opiates have a significant pharmacologic resemblance and may ultimately produce similar molecular events in the brain leading to the relief of pain.

Acetates↗
PubMed1976

Nitrous oxide "analgesia": resemblance to opiate action.

Nitrous oxide produced a dose-related "analgesia" in mice (median effective dose, 55 percent). The analgesia was evaluated by means of a phenylquinone writhing test. Narcotic antagonists or chronic morphinization reduced nitrous oxide analgesia. Either nitrous oxide releases an endogenous analgesic or narcotic antagonists have analgesic antagonist properties heretofore unappreciated.

Analgesia↗
PubMed1976

Disposition of propranolol isomers in mice.

l-Propranolol was found to protect mice from hyperbaric oxygen-induced seizures. The disposition of effective doses of propranolol isomers in mice was followed using stereospecific antibodies with a radioimmunoassay procedure. Serum and tissue concentrations were determined and correlated with the protective effect. Following racemic administration, there were no differences in serum disposition of d- and l-propranolol, although there was initially a preferential uptake of the 1-isomer both into cardiac and brain tissue. The d-isomer exerted synergistic action on the 1-isomer protective effect.

Animals↗
PubMed1976

Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action.

Using a specific and sensitive radioimmunoassay, naloxone concentrations in the brains and sera of rats were measured at intervals for four hours following iv injection (5 mg/kg). Decrement curves of naloxone were compared with those after iv injection of morphine (5 mg/kg). Serum concentration of naloxone at 5 minutes was 1.45 +/- 0.1 mug/ml (mean +/- SE) and that of morphine was 1.0 +/- 0.08 mug/ml. Their serum half-lives from one to four hours were approximately the same, 30-40 minutes. With naloxone, the brain-serum concentration ratios ranged from 2.7 to 4.6. Concentration of naloxone in the brain declined parallel to that in the serum. However, with morphine the initial brain concentration was approximately one tenth that in the serum (0.096 +/- 0.04 mug/ml). The brain morphine concentration was sustained for one hour, while serum morphine concentrations declined from 1.0 to 0.19 mug/ml during this period. Two minutes after iv injection of naloxone HCl (0.4 mg) in nine healthy volunteers, the serum drug concentration was 0.01 +/- .001 mug/ml. At 5 minutes, 97 per cent of the administered dose was no longer found in the serum, the serum concentration being 0.004 +/- .0003 mug/ml. From 20 minutes to two hours after injection, the calculated mean serum half-life of naloxone was 64 minutes. These results suggest that the rapid penetrance of naloxone into the brain and the high brain-serum concentration ratio contribute to its rapid onset of action and potency as a narcotic antagonist. The rapid decline of naloxone concentration in the brain found in the animal model, in contrast to that of morphine, could be the basis for its relatively short duration of action.

Adult↗
PubMed1975

The diposi tion of morphine in surgical patients.

The disposition of serum morphine following administration of 10 mg/70 kg was determined by a sensitive and specific radioimmunoassay in 31 anethetized surgical patients ranging in age from 23 to 75 yr. Following iv injection, 93 per cent of the morphine disappeared from the serum within 5 min. The early serum levels of the drug (2 min) correlated directly with the patients' ages (r equal to 0.63, p smaller than 0.01). Patient 23 to 50 yr of age averaged 0.29 mug/ml, whereas patients 51 to 75 ur of age averaged 70 percent higher, 0.49 mug/ml. The serum half-life between 10 and 240 min was independent of age and averaged about 2 hr after either iv or im administration. Following im admininstration, morphine was rapidly absorbed, with peak levels occurring within 10 to 20 min. The decline in morphine serum levels paralleled the decline in morphine analgesia and was coincident with the apperance of morphine glucuronide in the serum. These studies demonstrate the applicability and specificity of the radioimmunoassay for morphine and suggest that serum levels of morphine may be a useful and objective indicator of its pharmacologic activity.

Adult↗
PubMed1975

Disposition of naloxone: use of a new radioimmunoassay.

Understanding of the pharmacology of the narcotic antagonist naloxone has been limited by the lack of a convenient and sensitive method of assay. A radioimmunoassay for naloxone has been developed and is described. It is applicable for drug analysis in either serum or brain. The limit of sensitivity of the assay was 0.1 ng. Naloxone glucuronide, noroxymorphone (nor-naloxone) and morphine were not recognized by the antibody whereas naltrexone and 6-hydroxynaloxone were able to displace naloxone-3H from the antibody. The assay was of sufficient sensitivity to follow the serum levels of naloxone in man for up to 2 hours after an i.v. injection of 0.4 mg. In animal studies, the biologic half-lives of naloxone or morphine (5 mg/kg) were compared after s.c. injection in rats. The peak serum levels A (1 mu/mo), time to peak serum levels (less than 1/2 hour), and serum half-life (40 minutes) were comparable. However, the brain entry and egress of the two compounds differed markedly. Peak brain levels of naloxone occurred within 15 minutes and had declined by 50% within 1 hour, whereas the peak brain levels of morphine were sustained for up to 2 hours. At peak serum levels, the brain/serum ratio for morphine was 0.1 whereas for naloxone it was 15 times greater. We suggest the high brain/serum ratio of naloxone contributes to its potency whereas the rapid egress from the brain is important in the short duration of action of naloxone.

Animals↗