Computer simulation of quantal dose-response relationships.
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Computer-Assisted Instruction↗
Biomedical subjects
K L McGilliard
Publications and source records attributed to K L McGilliard.
Chloral hydrate and the carbon dioxide chemoreceptor response: a study of puppies and infants.
CO2 chemoreceptor function was assessed during natural sleep and following the administration of 100 mg/kg of chloral hydrate to 26 puppies. With chloral hydrate-induced sleep, there were no significant changes in ventilation or in CO2 chemoreceptor response. The ventilation and CO2 chemoreceptor response of a group of infants in natural sleep were compared with those of a group receiving 50 mg/kg of chloral hydrate. Tidal volume O2 consumption, and CO2 elimination were slightly higher in the group given chloral hydrate. There was no difference in the CO2 chemoreceptor response. The proportion of time spent in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in chloral hydrate-induced sleep was similar to that occurring in natural sleep. Use of chloral hydrate stabilizes O2 consumption sleep. Use of chloral hydrate stabilizes O2 consumption and CO2 production, and it greatly facilitates the assessment of chemoreceptor function in infants. The CO2 chemoreceptor response appears not to be altered in puppies or infants.
Animals↗
Stereospecific radioimmunoassay of alpha-l-acetylmethadol (LAAM).
A sensitive and specific radioimmunoassay has been developed which allows quantitation of picogram amounts of alpha-l-acetylmethadol (LAAM) in biological fluids without prior extraction. Antiserum was obtained from rabbits immunized with antigen prepared by conjugation of alpha-l-methadol hemisuccinate with thyroglobulin. The antiserum was stereospecific, distinguishing LAAM from its three stereoisomers. In addition, there was little cross-reaction in the assay by metabolites of LAAM and no interference with the assay by other narcotic analgesics. The sensitivity of the assay was 50 pg, requiring serum sample sizes as small as 10 microliters. The radioimmunoassay was used to determine serum concentrations of LAAM in five female dogs receiving i.v. injections of 2 mg/kg of LAAM. The decay of LAAM in serum appeared to be multiexponential, with a mean terminal half-life of 35 hr. The dogs were behaviorally depressed for at least 9 hr and hypothermic for at least 24 hr after injection. The persistence of these pharmacological effects was probably due to the slow elimination of LAAM and the presence of major metabolites which are pharmacologically active.
Animals↗
The effect of dopaminergic modifiers on morphine-induced analgesia and respiratory depression.
The influences of the dopaminergic system on morphine-induced analgesia and respiratory depression were compared using modulators of dopaminergic activity. Blockade of dopaminergic receptors by haloperidol or pimozide produced a potentiation of morphine analgesia, while stimulation of dopaminergic activity by L-dopa methyl ester inhibited morphine analgesia. Morphine-induced depression of respiratory rate was potentiated by haloperidol and inhibited by pimozide or L-dopa methyl ester. These results suggest that the dopaminergic system plays a modulating role in morphine-induced analgesia, but not in morphine-induced respiratory depression.
Analgesics, Opioid↗
Stereospecific radioimmunoassay of d- and 1-methadone.
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Animals↗
Antagonism by naloxone of narcotic-induced respiratory depression and analgesia.
Receptor mechanisms for narcotic-induced respiratory depression and analgesia were compared by apparent pA2 values of morphine-naloxone, levorphanol-naloxone and pentazocine-naloxone. The similarity of apparent pA2 values of the three compunds for respiratory depression suggests that morphine, levorphanol and pentazocine may interact with similar receptors to produce this effect. Significant differences between apparent pA2 values of pentazocine-naloxone and morphine-naloxone or levor-phanol-naloxone for analgesia suggest, as previously shown, that narcotic and narcotic-antagonist analgesics appear to interact with receptors in different manners. Significant differences between apparent pA2 values for respiratory depression and analgesia suggest that these two effects of the narcotic drugs are mediated by different receptor interactions.
Analgesics, Opioid↗
Alterations in the antagonism by naloxone of morphine-induced respiratory depression and analgesia after morphine pretreatment.
Mice were pretreated either acutely or chronically with morphine to test the effect of such pretreatments on the antagonism by naloxone of morphine-induced respiratory depression and analgesia and to compare the development of tolerance to the two effects. A s.c. injection of 20 mg/kg of morphine 6 hr before testing produced a shift of the apparent pA2 of morphine-naloxone for analgesia from 7.05 to 7.33, while the same pretreatment did not change the apparent pA2 for respiratory depression. However, s.c. implantation of a morphine pellet for 72 hr produced a shift in the apparent pA2 of morphine-naloxone for respiratory depression from 7.35 to 7.63, which represents less than a 2-fold increase in naloxone potency. The same pretreatment produced a further shift of the apparent pA2 for analgesia to 7.58, representing a greater than 3-fold increase in naloxone potency. After morphine pellet implantation mice showed a much greater degree of tolerance to morphine-induced analgesia than to respiratory depression. These results provide further evidence that narcotic-induced respiratory depression and analgesia are mediated by different receptor interactions.
Analgesics↗