Possible cocaine predisposition to adverse cerebrovascular and cardiovascular sequelae of bromocriptine administered postpartum.
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Adult↗
Biomedical subjects
L G Miller
Publications and source records attributed to L G Miller.
Tardive akathisia: an analysis of clinical features and response to open therapeutic trials.
In recent years, there has been increasing recognition that akathisia occurs not only as an acute, self-limited complication of dopamine (DA) antagonist treatment, but also as a persistent form, called tardive akathisia. We represent a retrospective analysis of clinical features and therapeutic trials in 52 cases of this disorder. Although most patients developed this disorder after years of DA antagonist treatment (mean = 4.5 years), a significant proportion (34%) developed it within 1 year. The characteristic motor features included frequent, complex stereotyped movements. The legs were most frequently involved, showing marching in place and crossing/uncrossing. Trunk rocking, respiratory grunting and moaning, and complex hand movements such as face rubbing or scratching also occurred. In the 26 patients who were able to discontinue DA antagonists, akathisia persisted for years (mean = 2.7 years, range of 0.3-7 years) until abatement of symptoms or last follow-up. Younger patients were more likely to have remission or therapeutic suppression of akathisia at follow-up. In our experience, the catecholamine-depleting drugs reserpine and tetrabenazine were the most effective agents for suppressing symptoms, producing improvement in 87 and 58% of patients treated, respectively. However, improvement was limited in many patients, and at last follow-up only 33% of patients had complete abatement of their symptoms. In conclusion, tardive akathisia is a particularly disabling form of tardive dyskinesia, frequently persistent for years and often resistant to therapy.
Adult↗
MIF-1 and Tyr-MIF-1 fail to alter benzodiazepine-induced hypothermia.
Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) can increase GABA-stimulated benzodiazepine binding in brain tissue can block the hypothermia induced by several other compounds. Since benzodiazepines can also cause hypothermia, colonic temperatures were measured in mice after administration of chlordiazepoxide (CDP) and these two brain peptides. In several experiments involving different doses and times of administration of CDP, MIF-1, and Tyr-MIF-1, there were no significant effects of the peptides in altering the reliable decrease in colonic temperature induced by the benzodiazepine. The results indicate that the interaction of Tyr-MIF-1 and MIF-1 with benzodiazepines does not involve thermoregulation.
Animals↗
Persistent alterations in GABAA receptor binding and function after prenatal lorazepam administration in the chick.
Behavioral abnormalities have been reported in young and adult animals exposed to benzodiazepines prenatally. The presence of neurochemical alterations in the GABAergic system after prenatal benzodiazepine exposure was assessed in a chick model which avoids prenatal and postnatal maternal effects. The GABAA receptor complex, the presumed site of benzodiazepine action, was altered in adult chickens previously exposed to lorazepam for 10 days in ovo. Binding was decreased at the putative chloride channel site labeled by [35S]TBPS, coupling was decreased between this site and the GABA binding site, and function of the GABAA receptor in chloride uptake was diminished in animals exposed to prenatal lorazepam. Persistent neurochemical alterations in the GABAergic system accompany prenatal benzodiazepine exposure, and may influence subsequent behavior and development.
Animals↗
MIF-1 and Tyr-MIF-1 augment muscimol-stimulated chloride uptake in cerebral cortex.
The peptides MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) recently have been found to augment the effects of gamma-aminobutyric acid (GABA) on benzodiazepine receptor binding and chloride channel binding (Tyr-MIF-1) at the GABAA receptor complex. To determine whether these peptides affect the function of this complex in chloride transport, we evaluated chloride uptake stimulated by the GABA analog muscimol in synaptoneurosome preparations. In mice treated with either MIF-1 or Tyr-MIF-1 (1 mg/kg IP), maximal chloride uptake in cortex was increased compared with controls. The two peptides had similar effects in cortical preparations, but in cerebellum neither peptide altered chloride uptake. No differences from controls were observed in cortical synaptoneurosomes treated in vitro with either MIF-1 or Tyr-MIF-1. These results suggest that the brain peptides MIF-1 and Tyr-MIF-1 alter function at the GABAA receptor complex, perhaps by binding at a specific peptide receptor.
Animals↗
Differential effects of Tyr-MIF-1 and naloxone in two animal models involving benzodiazepine.
It has been shown previously that the endogenous brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) can act as an antiopiate and can also increase binding and function at the GABAA/benzodiazepine receptor complex. We now describe the effects of this tetrapeptide in two models in which the antiopiate naloxone has been reported to decrease the activity of benzodiazepines. Unlike naloxone, Tyr-MIF-1 and MIF-1 neither prevented chlordiazepoxide-induced locomotor hyperactivity in mice on a tilting floor nor suppressed chlordiazepoxide-induced eating in rats. Thus, in these two systems, Try-MIF-1 did not act as an antiopiate or alter the effects of a benzodiazepine, indicating a selectivity in the actions of Tyr-MIF-1.
Animals↗
Lorazepam discontinuation promotes 'inverse agonist' effects of benzodiazepines.
1. The effects of lorazepam discontinuation on responses to benzodiazepine agonists and antagonists were studied in mice. 2. The convulsant dose of pentylenetetrazol was decreased after an acute dose of lorazepam (0.5 mg kg-1) at 4 days after drug discontinuation, compared to 1 or 7 days after discontinuation or to vehicle treatment. 3. The percentage of mice undergoing convulsions after an acute dose of FG 7142 (40 mg kg-1) was increased at 4 days after lorazepam discontinuation, compared to 1 or 7 days after discontinuation or to vehicle treatment. 4. After an acute dose (0.5 mg kg-1), lorazepam concentrations in cortex tended to be greater in lorazepam-treated compared to vehicle-treated mice at 4 days after discontinuation compared to 1 and 7 days. 5. These data indicate a shift toward reduced agonist sensitivity and increased inverse agonist sensitivity in mice 4 days after lorazepam discontinuation.
Animals↗
Selenate reduction to elemental selenium by anaerobic bacteria in sediments and culture: biogeochemical significance of a novel, sulfate-independent respiration.
Interstitial water profiles of SeO(4), SeO(3), SO(4), and Cl in anoxic sediments indicated removal of the seleno-oxyanions by a near-surface process unrelated to sulfate reduction. In sediment slurry experiments, a complete reductive removal of SeO(4) occurred under anaerobic conditions, was more rapid with H(2) or acetate, and was inhibited by O(2), NO(3), MnO(2), or autoclaving but not by SO(4) or FeOOH. Oxidation of acetate in sediments could be coupled to selenate but not to molybdate. Reduction of selenate to elemental selenium was determined to be the mechanism for loss from solution. Selenate reduction was inhibited by tungstate and chromate but not by molybdate. A small quantity of the elemental selenium precipitated into sediments from solution could be resolublized by oxidation with either nitrate or FeOOH, but not with MnO(2). A bacterium isolated from estuarine sediments demonstrated selenate-dependent growth on acetate, forming elemental selenium and carbon dioxide as respiratory end products. These results indicate that dissimilatory selenate reduction to elemental selenium is the major sink for selenium oxyanions in anoxic sediments. In addition, they suggest application as a treatment process for removing selenium oxyanions from wastewaters and also offer an explanation for the presence of selenite in oxic waters.
Journal Article↗
A case of fluoxetine-induced serum sickness.
After 3-4 weeks of taking fluoxetine for depression, a 27-year-old man developed fever, skin eruptions, arthralgia, and lymphadenopathy. His clinical symptoms and results of laboratory assessment were consistent with a diagnosis of serum sickness reaction to the fluoxetine.
Adult↗
Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics.
With the ever-increasing population of cigarette smokers, the potential for cigarette smoke to affect drug therapy both pharmacokinetically and pharmacodynamically is significant. The overriding pharmacokinetic effect is increased drug metabolism through the induction of liver enzymes. The constituents of tobacco smoke, primarily nicotine, have their own pharmacological effects which may potentiate or antagonise the desired pharmacological effect of a particular drug, thereby affecting its efficacy. Furthermore, end-organ responsiveness may also be altered by tobacco. These latter 2 aspects constitute altered clinical pharmacodynamics. Approximately 30 drugs have been evaluated in terms of cigarette smoking. Induction of liver enzymes has been shown to increase the metabolism of imipramine, meprobamate, oestrogens, pentazocine, phenylbutazone, theophylline and warfarin. Nicotine has been shown to inhibit diuresis, alter ulcer healing, impair subcutaneous absorption, affect protein binding and stimulate catecholamine release; these effects have been evaluated in terms of therapy with frusemide (furosemide), histamine H2-antagonists, insulin, lignocaine (lidocaine) and beta-blockers, respectively. The interactions have not been correlated with clinical significance in all cases. Diminished end-organ responsiveness may account for reduced drowsiness in smokers receiving chlorpromazine and benzodiazepines, compared with non-smokers. Smoking has been associated with diminished pain tolerance, requiring increased dosages of morphine, pethidine (meperidine) and propoxyphene. Enzyme-inducers such as carbamazepine, phenytoin and phenobarbitone appear to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already maximally stimulated. Codeine, corticosteroids and nortriptyline do not appear to be affected by cigarette smoke. The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy. The effect of smoking on paracetamol (acetaminophen) has been variable, depending on the extent of smoking, and does not appear to be of clinical significance.
Animals↗
Indomethacin-associated sexual dysfunction.
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Back Pain↗
Dietary choline intake modulates benzodiazepine receptor binding and gamma-aminobutyric acidA receptor function in mouse brain.
Several lines of evidence suggest that dietary choline intake influences the metabolism of membrane phospholipids with possible effects on GABAergic neurotransmission. Based on these findings, the present experiments determined whether chronic choline supplementation or deficiency alters GABAergic function at the level of the gamma-aminobutyric acid (GABA)/benzodiazepine-chloride channel complex. To accomplish this, mice were fed diets containing 0% (deficient), 0.2% (basal) or 2.0% (supplemented) choline chloride for 28 days, and behavior, ligand binding at several sites in the complex and chloride uptake were determined in various brain regions. For both rotarod ataxia and open-field activity, mice receiving choline supplementation had a decreased response to clonazepam compared to those receiving basal and deficient diets. Choline supplementation significantly increased the in vivo binding of [3H]Ro15-1788 to cortex and cerebellum by 19% and 24%, respectively, and in vitro studies in cortical membranes indicated a significant 36% increase in the maximal number of [3H]flunitrazepam binding sites without a change in affinity, as compared to basal controls. In contrast, [3H]Ro15-1788 binding in vivo in all brain regions from mice fed the deficient diet decreased significantly to 20 to 58% of control values. Dietary choline intake did not alter GABA levels in brain, the binding of [35S]t-butylbicyclophosphorothionate to the chloride channel or the coupling between GABA and either the t-butylbicyclophosphorothionate site or the benzodiazepine site. However, the function of the GABAA receptor, determined by muscimol-stimulated chloride uptake into cortical synaptoneurosomes, was increased significantly in tissue from the supplemented group as compared to both control and deficient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chronic benzodiazepine administration. III. Upregulation of gamma-aminobutyric acidA receptor binding and function associated with chronic benzodiazepine antagonist administration.
Chronic administration of a benzodiazepine agonist appears to downregulate benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptor function. To examine the effects of chronic treatment with a benzodiazepine antagonist, we administered Ro15-1788, 1, 2 and 5 mg/kg/day to mice via implanted s.c. osmotic pumps for 1 to 14 days. Plasma and cortex (CX) concentrations of Ro15-1788 remained constant between days 1 and 7, indicating no change in pharmacokinetics. Open-field activity studies showed no change in distance traveled or ambulatory time at days 1, 2 and 4, but an increase in both parameters at days 7 and 14 in mice receiving Ro15-1788, 2 mg/kg/day. Benzodiazepine receptor binding was unchanged in CX, cerebellum (CB), hypothalamus, hippocampus and ponsmedulla at 1, 2 and 4 days at a dose of 2 mg/kg/day. Binding was increased in CX, CB and hippocampus at day 7 compared to days 1 and 2, and remained elevated at day 14. Similar results were observed at Ro15-1788 doses of 1 and 5 mg/kg/day. Benzodiazepine binding assessed in vitro in CX and CB also was increased at day 7 compared to day 1, due to an increase in receptor number rather than a change in apparent affinity. Binding of t-[35S]butylbicyclophosphorothionate to the chloride channel site in CX after Ro15-1788, 2 mg/kg/day, was increased at days 7 and 14 compared to days 1, 2 and 4 and controls due to an increase in number of binding sites. t-Butylbicyclophosphorothionate binding in CB was unchanged throughout.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chronic clonazepam administration decreases gamma-aminobutyric acidA receptor function in cultured cortical neurons.
Chronic benzodiazepine administration has been reported to decrease gamma-aminobutyric acidA (GABAA) receptor function in animals and may alter benzodiazepine binding in neuronal cultures. To assess GABAA receptor function in neuronal cultures exposed to chronic clonazepam, we measured muscimol-stimulated chloride uptake in chick cerebral cortical cultures treated acutely and for 2, 4, and 10 days. Acute clonazepam administration (1 microM) led to an increase in GABA-related chloride uptake at lower doses of muscimol. After chronic clonazepam (1 microM), maximal uptake was markedly decreased at day 10, but maximal uptake was unchanged after 2- and 4-day treatments. Benzodiazepine receptor binding was decreased by approximately 60% after 10 days due to a decrease in receptor number. Decreases in chloride uptake were also observed after 10 days of treatment with 0.1 and 10 microM clonazepam. Concomitant treatment with 0.1 microM Ro15-1788 abrogated the effect of 0.1 microM clonazepam on chloride uptake. Chronic clonazepam treatment (1 microM) did not alter total cellular protein, cellular protein synthesis or degradation or percentage of neuronal cells, as determined morphologically and by [3H]ouabain binding.
Animals↗
Prenatal lorazepam administration is associated with GABAA receptor alterations in late embryonic and mature chicks.
Prenatal benzodiazepine administration has been associated with alterations in behavior in young and mature animals. Prior studies of neurochemical changes in animals treated in utero have produced conflicting results. We used a chick embryo system to assess the effects of chronic lorazepam administration on binding and function at the GABAA receptor in late embryos and in mature animals. Administration of lorazepam for 10 days of embryonic development (E8-E18) led to decreases in binding of the chloride channel ligand TBPS and in muscimol-stimulated chloride uptake in late embryos (E18). Similar alterations were observed in mature animals after the same regimen of prenatal lorazepam. Persistent alterations in GABAA receptor binding and function after prenatal lorazepam may be due to effects of neuronal differentiation or on receptor regulation. These neurochemical effects may underlie the behavioral abnormalities associated with prenatal benzodiazepine administration.
Animals↗
Phenylpropanolamine: a controversy unresolved.
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Appetite↗
Sparing effect of sulindac on lithium levels.
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Aged↗
Lorazepam administration during embryonic development alters GABAA receptor binding and function.
Prenatal exposure to diazepam has been reported to lead to behavioral alterations in young and mature animals, but the neurochemical basis of this effect is uncertain. To examine effects of embryonic benzodiazepine exposure on the gamma-aminobutyric acidergic (GABA)ergic) system, we assessed binding and function at the GABAA receptor complex in chick embryos treated with lorazepam, 2 mg/kg, for 2-10 days. There was no change in benzodiazepine receptor binding in cortex after lorazepam administration, but a decrease in the number of chloride channel sites was observed. Overall function at the GABAA receptor complex as assessed by chloride uptake into cortical synaptoneurosomes was decreased after 10 days of lorazepam, and possibly increased after 4 days of lorazepam. Similar results were obtained when embryos were treated for 2- and 4-day periods beginning on day 8. These results indicate that chronic lorazepam administration to embryos alters binding and function in the GABA system measured soon before hatching. These alterations, if persistent, may contribute to the behavioral changes seen in animals exposed prenatally.
Animals↗