鏂囩尞鍒嗘瀽缁撴灉
midazolam and consciousness
鏈€鏂扮爺绌惰繘灞?/p>
2010 Feb 9;107(6):2681-6. Epub 2010 Jan 25.
, , , , , , , .
Department of Psychiatry and Anesthesiology, University of Wisconsin, Madison, WI 53719, USA.
Abstract
By employing transcranial magnetic stimulation (TMS) in combination with high-density electroencephalography (EEG), we recently reported that cortical effective connectivity is disrupted during early non-rapid eye movement (NREM) sleep. This is a time when subjects, if awakened, may report little or no conscious content. We hypothesized that a similar breakdown of cortical effective connectivity may underlie loss of consciousness (LOC) induced by pharmacologic agents. Here, we tested this hypothesis by comparing EEG responses to TMS during wakefulness and LOC induced by the benzodiazepine midazolam. Unlike spontaneous sleep states, a subject's level of vigilance can be monitored repeatedly during pharmacological LOC. We found that, unlike during wakefulness, wherein TMS triggered responses in multiple cortical areas lasting for >300 ms, during midazolam-induced LOC, TMS-evoked activity was local and of shorter duration. Furthermore, a measure of the propagation of evoked cortical currents (significant current scattering, SCS) could reliably discriminate between consciousness and LOC. These results resemble those observed in early NREM sleep and suggest that a breakdown of cortical effective connectivity may be a common feature of conditions characterized by LOC. Moreover, these results suggest that it might be possible to use TMS-EEG to assess consciousness during anesthesia and in pathological conditions, such as coma, vegetative state, and minimally conscious state.
PMID: 20133802 [PubMed - indexed for MEDLINE]PMCID: PMC2823915 [Available on 2010/8/9]
- [Science. 2005]
- [Neuroimage. 2010]
- [PLoS One. 2007]
- [Neurophysiol Clin. 2003]
- [Eur J Neurosci. 2009]
Midazolam - Compound Summary (CID )
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
Table of Contents
BioMedical Annotation: (Total:1)
Midazolam hydrochloride is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1mg or 5mg midazolam
Midazolam hydrochloride is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1 mg or 5 mg midazolam
Midazolam hydrochloride is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1 mg or 5 mg midazolam
Midazolam hydrochloride is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1 mg or 5 mg midazolam
Midazolam hydrochloride is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1 mg or 5 mg midazolam
Midazolam is a benzodiazepine available as midazolam hydrochloride syrup for oral administration. Midazolam, a white to light yellow crystalline compound, is insoluble in water, but can be solubilized in aqueous solutions by formation of
- Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage.
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- Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
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- Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.
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- Ultrashort-acting anesthetics that are used for induction. Loss of consciousness is rapid and induction is pleasant, but there is no muscle relaxation and reflexes frequently are not reduced adequately. Repeated administration results in accumulation and prolongs the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in brief minor procedures. (From AMA Drug Evaluations Annual, 1994, p174)
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- Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
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Pharmacological Classification
Chemical Classification
- Peer-reviewed summary of toxicity and biomedical effects
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- European Inventory of Existing Commercial Chemical Substances
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- European Inventory of Existing Commercial Chemical Substances
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- European Inventory of Existing Commercial Chemical Substances
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- Citations to the toxicological literature
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- Citations to the toxicological literature
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- Citations to the toxicological literature
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- Information on chemicals that breastfeeding mothers may be exposed
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- Registry of federal and private clinical trials
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Choose by Subheadings:
Properties Computed from Structure:
Molecular Weight |
328.745288 [g/mol] |
Molecular Formula |
C18H13ClFN3 |
XLogP3 |
2.5 |
H-Bond Donor |
0 |
H-Bond Acceptor |
3 |
Rotatable Bond Count |
1 |
Exact Mass |
328.088268 |
MonoIsotopic Mass |
328.088268 |
Topological Polar Surface Area |
30.2 |
Heavy Atom Count |
23 |
Formal Charge |
0 |
Complexity |
471 |
Isotope Atom Count |
3 |
Defined Atom StereoCenter Count |
0 |
Undefined Atom StereoCenter Count |
0 |
Defined Bond StereoCenter Count |
0 |
Undefined Bond StereoCenter Count |
0 |
Covalently-Bonded Unit Count |
1 |
Descriptors Computed from Structure:
IUPAC Name: 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1, 4]benzodiazepine Canonical SMILES: CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F Isomeric SMILES: [13CH3][13C]1=N[13CH]=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F InChI: InChIKey: DDLIGBOFAVUZHB-JVGDUDMDSA-N
Compound Information:
CID
Related Compounds:
Similar Compounds: Similar Conformers:
Substance Information:
Substances:
Category: [for same structure substances]
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