Related Experiment Video

Updated: Aug 30, 2026

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
09:16

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Published on: January 22, 2016

Metabolites of methohexitone do not contribute to its prolonged action on the central nervous system

K Korttila1, M M Ghoneim, C K Chiang

  • 1Department of Anesthesia and Critical Care, University of Chicago.

Acta Anaesthesiologica Scandinavica
|January 1, 1990
PubMed

Insights

Methohexitone

Area of Science:

  • Pharmacology
  • Neuroscience
  • Drug Metabolism

Background:

  • Methohexitone exhibits a prolonged central nervous system (CNS) effect despite a short elimination half-life.
  • The role of its metabolites in this prolonged CNS activity requires investigation.

Purpose of the Study:

  • To identify and characterize the central nervous system (CNS) activity of methohexitone's hydroxy metabolite.
  • To determine if this metabolite contributes to the prolonged CNS effects of methohexitone.

Main Methods:

  • Isolation and purification of methohexitone's hydroxy metabolite from human and canine urine.
  • Assessment of the metabolite's CNS-depressant activity in mice using a rotarod test.
  • Comparison of the ED50 of the metabolite with that of the parent drug, methohexitone.

Main Results:

  • A hydroxy metabolite of methohexitone was identified and isolated.
  • The metabolite demonstrated CNS-depressant activity, but with an ED50 ten times higher than methohexitone.
  • The hydroxy metabolite was undetectable in human blood and present at lower concentrations than methohexitone in canine plasma.

Conclusions:

  • The major hydroxy metabolite of methohexitone is unlikely to be responsible for its prolonged central nervous system (CNS) effects.
  • Further research may be needed to elucidate the mechanisms behind methohexitone's extended CNS action.

More Related Videos

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry10:17

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry

Published on: April 23, 2019

Fentanyl Analog Screening using LC-TIMS-TOF MS/MS10:13

Fentanyl Analog Screening using LC-TIMS-TOF MS/MS

Published on: November 8, 2024

Related Concept Videos

Adrenergic Agonists: Indirect-Acting Agents01:25

Adrenergic Agonists: Indirect-Acting Agents

Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Adrenergic Agonists: Mixed-Action Agents01:28

Adrenergic Agonists: Mixed-Action Agents

Mixed-action adrenergic agonists, like ephedrine and pseudoephedrine, directly and indirectly affect adrenergic receptors. These agents stimulate adrenoceptors and indirectly release stored neurotransmitters, amplifying the adrenergic response.
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics01:11

Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics

All neuromuscular blocking agents are injected intravenously because they are poorly absorbed from the GI tract. Rapid onset is achieved with intravenous administration, although absorption is also adequate from an intramuscular injection. Since these agents are highly ionized, they do not readily penetrate cell membranes or cross the blood-brain barrier.
Instead, they are transported by the blood to different tissues. Muscles with a greater blood supply (arteries) and blood flow receive more...
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
Sedatives and Hypnotics Drugs: Miscellaneous Agents01:17

Sedatives and Hypnotics Drugs: Miscellaneous Agents

Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...