Identification

Name
Paraldehyde
Accession Number
DB09117
Type
Small Molecule
Groups
Approved, Investigational
Description

Paraldehyde is the cyclic trimer of acetaldehyde molecules. It was introduced into clinical practice in the UK by the Italian physician Vincenzo Cervello in 1882. It is a central nervous system depressant and was soon found to be an effective anticonvulsant, hypnotic and sedative. It was included in some cough medicines as an expectorant (though there is no known mechanism for this function beyond the placebo effect).

Structure
Thumb
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paraldehyde Inj Bp 100%Liquid100 %Intramuscular; IntravenousDavid Bull Laboratories (Pty) Ltd.1991-12-311999-08-10Canada
Paraldehyde Injection BPLiquid100 %Intramuscular; IntravenousOmega Laboratories Ltd2012-02-082015-12-11Canada
Paraldehyde Injection BPLiquid100 %Intramuscular; IntravenousPharmascience Inc1998-09-102013-03-14Canada
Categories
UNII
S6M3YBG8QA
CAS number
123-63-7
Weight
Average: 132.1577
Monoisotopic: 132.07864425
Chemical Formula
C6H12O3
InChI Key
SQYNKIJPMDEDEG-UHFFFAOYSA-N
InChI
InChI=1S/C6H12O3/c1-4-7-5(2)9-6(3)8-4/h4-6H,1-3H3
IUPAC Name
2,4,6-trimethyl-1,3,5-trioxane
SMILES
CC1OC(C)OC(C)O1

Pharmacology

Indication

Paraldehyde was used historically as a sedative and hypnotic [1]. It has been used in the treatment of seizures as an anticonvulsant [2].

Pharmacodynamics

Paraldehyde blocks neuromuscular transmission [3].

Mechanism of action

Paraldehyde is believed to reduce the release of acetylcholine in response to neuronal depolarization [3]. The exact mechanism of this effect is unknown.

Absorption

93% of orally administered paraldehyde is absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Paraldehyde is believed to undergo depolymerization to acetaldehyde followed by oxidation by aldehyde dehydrogenase [A19378]. It is thought to ultimately be metabolized to carbon dioxide and water.

Route of elimination

70-80% is metabolized to carbon dioxide and subsequently exhaled [4]. 11-28% is exhaled as the parent compound. 0.1-2.5% is excreted in the urine as the parent compound.

Half life

The mean half life is 7.5 hours in a range if 3.5-9.5 hours [4].

Clearance
Not Available
Toxicity

Paraldehyde overdosage can produce headache, nausea, drowsiness, unconsciousness, coma, severe hypotension, respiratory depression, pulmonary edema and hemorrhages, and right-side heart failure [4]. Inhalation of paraldehyde can produce sore throat, headache, dizziness, nausea, drowsiness and unconsciousness but exposure via this route is rare. Chronic use is dependence forming and withdrawal proceeds similarly to ethanol withdrawal producing hallucinations and convulsions. Toxic hepatitis and nephritis have been observed during chronic use.

The acute LD50 values determined for various species are as follows [4]:

Rabbit - 3.3-5 g/kg (oral) Rat - 1.5-1.65 g/kg (oral), 1.3-1.45 g/kg (i.p.) Dog - 3-4 g/kg (oral) Mouse - 2.75 (oral) Cat - 3.3 (oral)

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
3-isobutyl-1-methyl-7H-xanthineParaldehyde may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
6-O-benzylguanineParaldehyde may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-DeazaguanineParaldehyde may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Food Interactions
Not Available

References

General References
  1. Lopez-Munoz F, Ucha-Udabe R, Alamo C: The history of barbiturates a century after their clinical introduction. Neuropsychiatr Dis Treat. 2005 Dec;1(4):329-43. [PubMed:18568113]
  2. Rowland AG, Gill AM, Stewart AB, Appleton RE, Al Kharusi A, Cramp C, Yeung LK: Review of the efficacy of rectal paraldehyde in the management of acute and prolonged tonic-clonic convulsions. Arch Dis Child. 2009 Sep;94(9):720-3. doi: 10.1136/adc.2009.157636. Epub 2009 Apr 8. [PubMed:19357123]
  3. NICHOLLS JG, QUILLIAM JP: The mechanism of action of paraldehyde and methylpentynol on neuromuscular transmission in the frog. Br J Pharmacol Chemother. 1956 Jun;11(2):151-5. [PubMed:13329331]
  4. Von Burg R, Stout T: Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81. [PubMed:1783744]
External Links
Human Metabolome Database
HMDB0032456
KEGG Compound
C07834
PubChem Compound
31264
PubChem Substance
310265034
ChemSpider
21106173
ChEBI
27909
ChEMBL
CHEMBL1410743
Wikipedia
Paraldehyde
ATC Codes
N05CC05 — Paraldehyde
MSDS
Download (89.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentConvulsions / Refractory seizure disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntramuscular; Intravenous100 %
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)12Von Burg R, Stout T: Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81.
boiling point (°C)124Von Burg R, Stout T: Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81.
water solubility125g/LVon Burg R, Stout T: Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81.
logP0.73MSDS
Predicted Properties
PropertyValueSource
Water Solubility177.0 mg/mLALOGPS
logP0.33ALOGPS
logP0.88ChemAxon
logS0.13ALOGPS
pKa (Strongest Basic)-4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.69 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity32.09 m3·mol-1ChemAxon
Polarizability14.15 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0005-9000000000-a3f03c0baa80a3369e84
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as trioxanes. These are compounds containing a six-member aliphatic saturated heterocycle made up of three oxygen atoms and three carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Trioxanes
Sub Class
Not Available
Direct Parent
Trioxanes
Alternative Parents
Oxacyclic compounds / Acetals / Hydrocarbon derivatives
Substituents
1,3,5-trioxane / Oxacycle / Acetal / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Aliphatic heteromonocyclic compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
trioxane (CHEBI:27909)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Electron carrier activity
Specific Function
Not Available
Gene Name
ALDH2
Uniprot ID
P05091
Uniprot Name
Aldehyde dehydrogenase, mitochondrial
Molecular Weight
56380.93 Da
References
  1. Von Burg R, Stout T: Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81. [PubMed:1783744]

Drug created on September 22, 2015 13:31 / Updated on November 02, 2018 06:58