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Biomedical subjects

A Livingston

Publications and source records attributed to A Livingston.

At least 55 records · Page 3Linked to original sources
PubMed1988

Analgesic effects of intrathecally-applied alpha 2-adrenoceptor agonists in conscious, unrestrained sheep.

Intrathecal injections of small volumes of the alpha 2-adrenoceptor agonists, xylazine and clonidine, into the cervical region of the spinal cord of conscious unrestrained sheep produced a dose-dependent analgesia of the forelimbs as measured using a mechanical pressure device. Intravenous injection of the alpha 2-adrenoceptor antagonist, idazoxan completely abolished the analgesic effects of the intrathecally applied alpha 2-adrenoceptor agonists. Subsequent studies using [3H] clonidine injected at a similar dose and volume via the intrathecal catheters, indicated that the volume of drug used, 100 microliter, gave a localisation of the drug limited to about five vertebral segments around the catheter tip.

Adrenergic alpha-Agonists↗
PubMed1988

The correlation of the thermal and mechanical antinociceptive activity of pethidine hydrochloride with plasma concentrations of the drug in sheep.

The analgesic activity of pethidine was measured in eight sheep using both thermal and mechanical test systems. Pethidine, at a dose rate of 5 mg/kg body weight given intravenously, produced a significant degree of antinociception to thermal pain for 30 min (on average) but gave only a few minutes of significant analgesia when tested in the mechanical pressure system. Analgesia in both systems was abolished by pretreatment with naloxone. Pharmacokinetic analyses of plasma levels of pethidine after intravenous (i.v.) injection were carried out. Plasma concentrations of the drug exhibited a rapid biexponential pattern of decline with an average distribution half-life of 0.99 min and an elimination half-life of 12.8 min. Correlation of plasma levels of the drug with the presence of a significant degree of antinociception in the thermal test system enabled 'critical' analgesic levels of pethidine to be defined for sheep (0.93 microgram/ml).

Analgesia↗
PubMed1987

Influence of idazoxan on the respiratory blood gas changes induced by alpha 2-adrenoceptor agonist drugs in conscious sheep.

Administration of either xylazine (50 micrograms/kg) or detomidine (10 micrograms/kg) caused a significant degree of arterial hypoxaemia in six conscious sheep. This effect was independent of any changes produced by changes in posture as all the sheep remained standing. Administration of the specific alpha 2-antagonist drug idazoxan (0.1 mg/kg bodyweight) five minutes before injection of either of the drugs completely abolished the hypoxaemia. These results lend support to the view that the respiratory effect of these drugs is mediated via alpha 2-adrenoceptor activity.

Adrenergic alpha-Antagonists↗
PubMed1987

Techniques for comparison of thermal and mechanical nociceptive stimuli in the sheep.

The assessment of analgesia in conscious unrestrained farm animals presents particular problems. In order to provide a reliable nociceptive stimulus, two devices have been constructed, one that provides a threshold reading for a ramped thermal stimulus of the pinna of the ear and another that measures a threshold reading for a pressure stimulus to the foreleg. Both devices allow the rapid termination of the stimulus once a reaction has occurred and allow repeated readings without causing tissue damage. Examples of the analgesic action of alpha 2-adrenoceptor agonists and opioids measured by using the two pieces of apparatus are shown.

Animals↗
PubMed1987

Antinociceptive actions of intravenous alpha 2-adrenoceptor agonists in sheep.

The antinociceptive activity of the intravenously administered alpha 2-adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 micrograms/kg i.v. was more potent and longer lasting than xylazine at 50 micrograms/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1987

Investigation of the antinociceptive activity of buprenorphine in sheep.

1. Buprenorphine given intravenously (6 micrograms kg-1) was examined for its antinociceptive activity in unrestrained sheep using devices to measure thermal and mechanical thresholds. 2. The plasma levels of buprenorphine following intravenous injection over the time period of the antinociceptive testing were measured using a radioimmunoassay. 3. Buprenorphine produced a clear antinociceptive effect lasting for up to three and a half hours when measured by the thermal threshold test, but no detectable antinociception in the mechanical test. 4. The plasma levels of buprenorphine indicated that the drug was rapidly distributed in a manner not dissimilar to that reported in man, although individual animals showed a wide variation in some parameters. 5. When plasma levels of the drug were high (less than 700 pg ml-1) during the first sixty minutes, no antinociceptive activity in the thermal test could be detected, which may be due to the slow receptor kinetics shown by this drug.

Analgesics↗
PubMed1987

Autoradiographic localisation of alpha 2 adrenoceptor binding sites in the spinal cord of the sheep.

Alpha 2 adrenoceptor agonists, such as xylazine and detomidine, are used as sedatives, analgesics and premedicants. In this study the localisation of binding sites for alpha 2 agonist drugs in the sheep spinal cord was examined using [3H] clonidine as a ligand and autoradiographic techniques related to our initial histological mapping of the various tracts and laminae. The results indicated a high concentration of binding sites for alpha 2 adrenoceptor agonists in the lamina II region of the dorsal horn of the spinal cord (the substantia gelatinosa) which is an area widely implicated in the transmission of painful stimuli. Possibly therefore some of the analgesic effect of this group of drugs in sheep is mediated at the spinal level.

Adrenergic alpha-Agonists↗
PubMed1986

Localisation of [3H] clonidine binding in rat neurohypophysis by means of electron-microscopic autoradiography.

Electron-microscopic autoradiography of rat neurohypophyses treated with [3H] clonidine, an alpha 2-agonist, showed that binding apparently occurred preferentially at the neurosecretory endings and blood vessels rather than on the pituicytes. Since it is known that clonidine has a high affinity for plasma proteins, the distribution over the neurosecretory nerve endings would suggest the existence of presynaptic alpha 2-binding sites on neurosecretory neurones, which could indicate a regulatory function for catecholamines in neurohypophysial hormone release.

Animals↗
PubMed1986

The effects of alpha 2 adrenoceptor agonists on airway pressure in anaesthetized sheep.

Xylazine and clonidine, given intravenously, cause an increase in airway pressure in the anaesthetized, ventilated sheep. This increase was dose dependent and was not mediated by histamine, nor was it blocked by the alpha 1-adrenoceptor antagonist prazosin. However, the increase was abolished by the alpha 2-adrenoceptor antagonist, idazoxan. When the alpha 2-adrenoceptor agonists were administered into the cerebrospinal fluid by injection into the cisterna magna there was no increase in airway pressure, although a similar dose given peripherally still produced an effect. These findings would indicate that the increase in airway pressure seen in these sheep, following administration of xylazine and clonidine, was mediated by peripherally located alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1986

Developmental regression as an early manifestation of vitamin B12 deficiency.

Loss of previously attained developmental milestones in an infant is often associated with central nervous system tumor, neuromuscular disease, or an inborn metabolic error. An infant with developmental regression and involuntary movements who was found to be vitamin B12 deficient on the basis of unrecognized maternal vitamin B12 deficiency is described. The infant had a dramatic neurologic recovery after receiving vitamin B12. The case and a review of similar cases is presented.

Anemia, Macrocytic↗
PubMed1986

Release of i-r metenkephalin from rat amygdala slices in vitro.

Release of immuno-reactive metenkephalin has been demonstrated from slices of rat amygdala in vitro. This release was calcium dependent and the amount released was related to the concentration of potassium ions in the releasing stimulus. The effect of drugs such as clonidine, an alpha 2 adrenoceptor agonist, and idazoxan, an antagonist, on this release was measured. Neither drug had a significant effect on the amount of ir-metenkephalin released. Thus although release of noradrenaline can be affected by opioids it seems that release of endogenous opioids is not affected by drugs which interact with noradrenaline.

Adrenergic beta-Antagonists↗
PubMed1984

Autoradiographic demonstration of alpha 2 adrenoceptors in the bovine neurohypophysis.

Autoradiography of sections from neurohypophyses treated with tritiated clonidine has shown specific binding to alpha 2-adrenoceptor sites in the neurohypophysis but not in the intermediate lobe. Other studies have shown that alpha 2 agonists such as clonidine can cause a fall in circulating antidiuretic hormone; it is therefore possible to speculate that this action could be a direct one on the neurohypophysis since the appropriate binding sites have been shown to exist.

Animals↗
PubMed1984

Binding of [3H]clonidine to membranes from cow neurohypophysis and cerebral cortex of the rat.

The binding of [3H]clonidine to membranes prepared from rat cerebral cortex and cow neurohypophysis was compared. Both tissues showed a high affinity site and a low affinity site when examined using a variety of techniques. The binding data, together with displacement studies using a variety of alpha 2-adrenoceptor agonists and antagonists, indicated that the binding activity of clonidine in the two tissues was very similar, however when the putative sigma opiate compound SKF 10,047 was examined it was found to have only a weak activity in displacing clonidine on the cortical membranes but a much stronger activity on the neurohypophysial membranes, other opiates showed little activity on binding of clonidine in either tissue. It is proposed that the binding of clonidine to neurohypophysial membranes may explain in part the various reports of suppression by clonidine of release of hormones from the neurohypophysis and that the effects of SKF 10,047 may be similarly associated with the reports of diuresis induced by phencyclidine.

Adrenergic alpha-Agonists↗
PubMed1984

Effects of clonidine and xylazine on body temperature in the rat.

Clonidine and xylazine injected intraperitoneally both produced a dose-dependent hypothermia in unanaesthetized, freely moving rats. The alpha 2-antagonist yohimbine produced an antagonism of the xylazine-induced hypothermia but a potentiation of the clonidine-induced hypothermia. The opioid antagonist naloxone had little effect on the xylazine hypothermia, but potentiated the clonidine hypothermia. It is concluded that whilst the two alpha 2-agonists produce a similar hypothermic effect in the rat, they are acting by different mechanisms.

Animals↗