Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Space motion sickness (SMS) is a problem during the first 72 h of space flight and during transitions from different gravity environments. There currently are no effective drug countermeasures for SMS that also accommodate the retention of optimal cognitive function. This creates a dilemma for astronauts because cognitive skills are particularly important during gravity transitions (e.g., take-off and landing). To quantify the cognitive side effects of potential drug countermeasures, an automated delayed matching-to-sample (DMTS) procedure was used to assess visual working memory before and after drug countermeasures (meclizine 25 mg, scopolamine 0.4 mg, promethazine 25 mg, or lorazepam 1 mg, given orally approximately 45 min prior to testing) and/or the induction of SMS by vestibular stimulation in a rotary chair (spinning). Sixty-seven normal healthy volunteers (mean age, in years, 26.6+/-4.8 S.D.; 24 females and 43 males) each participated in two test sessions, one 'off' drug and one 'on' drug. Spinning by itself significantly decreased task accuracy (Acc) and choice response speed, especially at longer recall delays. Meclizine alone had no effect on Acc or speed with or without spinning. Scopolamine alone decreased Acc, and with spinning, slowed speed. Promethazine alone had no adverse effect, but combined with spinning, decreased Acc and speed. Lorazepam alone decreased speed, and with spinning, decreased Acc. The data suggest that, at clinically useful doses, the rank order of the drugs with the best cognitive profiles is meclizine>scopolamine>promethazine>lorazepam.
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PMID:Effects of drug countermeasures for space motion sickness on working memory in humans. 1545 Oct 46

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine] competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity, primarily for its effect on the eye, gastrointestinal tract, heart, and salivary and bronchial secretion glands, and in special circumstances for a CNS action. Therefore, scopolamine is most suitable for premedication before anesthesia and for antiemetic effects. This alkaloid is the most effective single agent to prevent motion sickness. Scopolamine was the first drug to be made commercially available in a transdermal therapeutic system (TTS-patch) delivering alkaloid. Recently, pharmacokinetic data on scopolamine in different biozlogic matrices were obtained most efficiently using liquid chromatographic-tandem mass spectrometric (LC-MS/MS) or gas chromatography online coupled to mass spectrometry. Pharmacokinetic parameters are dependent on the dosage form (oral dose, tablets; parenteral application; IV infusion; SC and IM injection). Scopolamine has a limited bioavailability if orally administered. The maximum drug concentration occurs approximately 0.5 hours after oral administration. Because only 2.6% of nonmetabolized L-(-)-scopolamine is excreted in urine, a first-pass metabolism is suggested to occur after oral administration of scopolamine. Because of its short half-life in plasma and dose-dependent adverse effects (in particular hallucinations and the less serious reactions, eg, vertigo, dry mouth, drowsiness), the clinical use of scopolamine administered orally or parenterally is limited. To minimize the relatively high incidence of side effects, the transdermal dosage form has been developed. The commercially available TTS-patch contains a 1.5-mg drug reservoir and a priming dose (140 microg) to reach the steady-state concentration of scopolamine quickly. The patch releases 0.5 mg alkaloid over a period of 3 days (releasing rate 5 microg/h). Following the transdermal application of scopolamine, the plasma concentrations of the drug indicate major interindividual variations. Peak plasma concentrations (Cmax) of approximately 100 pg/mL (range 11-240 pg/mL) of the alkaloid are reached after about 8 hours and achieve steady state. During a period of 72 hours the plaster releases scopolamine, so constantly high plasma levels (concentration range 56-245 pg/mL) are obtained, followed by a plateau of urinary scopolamine excretion. Although scopolamine has been used in clinical practice for many years, data concerning its metabolism and the renal excretion in man are limited. After incubation with beta-glucuronidase and sulfatase, the recovery of scopolamine in human urine increased from 3% to approximately 30% of the drug dose (intravenously administered). According to these results from enzymatic hydrolysis of scopolamine metabolites, the glucuronide conjugation of scopolamine could be the relevant pathway in healthy volunteers. However, scopolamine metabolism in man has not been verified stringently. An elucidation of the chemical structures of the metabolites extracted from human urine is still lacking. Scopolamine has been shown to undergo an oxidative demethylation during incubation with CYP3A (cytochrome P-450 subfamily). To inhibit the CYP3A located in the intestinal mucosa, components of grapefruit juice are very suitable. When scopolamine was administered together with 150 mL grapefruit juice, the alkaloid concentrations continued to increase, resulting in an evident prolongation of tmax (59.5 +/- 25.0 minutes; P < 0.001). The AUC0-24h values of scopolamine were higher during the grapefruit juice period. They reached approximately 142% of the values associated with the control group (P < 0.005). Consequently, the related absolute bioavailabilities (range 6% to 37%) were significantly higher than the corresponding values of the drug orally administered together with water (range 3% to 27%). The effect of the alkaloid on quantitative electroencephalogram (qEEG) and cognitive performance correlated with pharmacokinetics was shown in studies with healthy volunteers. From pharmacokinetic-pharmacodynamic modeling techniques, a direct correlation between serum concentrations of scopolamine and changes in total power in alpha-frequency band (EEG) in healthy volunteers was provided. The alkaloid readily crosses the placenta. Therefore, scopolamine should be administered to pregnant women only under observation. The drug is compatible with nursing and is considered to be nonteratogenic. In conclusion, scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting associated with motion sickness. Pharmacokinetics and pharmacodynamics of scopolamine depend on the dosage form. Effects on different cognitive functions have been extensively documented.
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PMID:Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. 1617 41