Thiopental

John A. Davies University of Wales College of Medicine, Cardiff, UK

ã 2007 Elsevier Inc. All rights reserved.

Introduction

Thiopental is a barbiturate widely used as an intravenous agent for the rapid induction of
general anesthesia, with consciousness being lost within 10–20 seconds. However, its
use as an inducing agent is decreasing following the introduction of propofol. Although
thiopental has a relatively long half-life of ~ 9 hours, it is a short-acting, highly lipid-
soluble compound. Its short duration of action is due to redistribution into muscle
and eventually fat Marshall and Longnecker (1996). Its mechanism of action is through
potentiation of GABAergic transmission via GABAA receptors Lingamaneni and
Hemmings (2003).

Nomenclature
Name of the Clinical Thiopental sodium
Form
Related Names Thiopental; 5 ethyl 5 (1 methylbutyl)2 thiobarbiturate sodium; 5
Source: EMTREE ethyl 5 (1 methylbutyl) 2 thiobituric acid; farmotal; hypnostan;
intraval; leopental; nesdonal; penthiobarbital; penthotal;
pentothal; pentothal sodium; pharmothal; ravonal; rp 245;
sodiumpentothal; sodium thiopental; thiomebumal;
thiomebumal sodium; thionembutal; thiopentalbarbital;
thiopental sodium; thiopentemal; thiopenthal;
thiopentobarbital; thiopentone; thiopentone sodium; thiotal;
thiothal; tiopentemal; trapanal; v 5; 5 ethyl 5 (1 methylbutyl)
2 thiobarbiturate sodium; sodium pentothal; tio pentemal
Chemical Names (R,S)-5-Ethyldihydro-5-(1-methylbutyl)-2-thioxo-4,6(1H,5H)-
pyrimidinedione
CAS Number 76-75-5

Basic Chemistry
Chemical Structure
Structure

Chemical Formula C11 H18 N2 O2 S

Properties

1
2 Thiopental

Physical Properties The sodium salt is a pale green, hygroscopic powder.

Molecular Weight 242.341
Solubility 1 in 1.5 in water
Ionization Constant
Value Salt Conditions Reference Comments
pKa 7.6 Sodium Dollery (1999)

Human Pharmacokinetics

Thiopental is bound to plasma proteins and is highly lipid soluble. It crosses the blood-
brain barrier very readily, and high levels are reached in the brain within seconds because
of the high blood supply. Within 1–2 minutes levels of thiopental in the brain decrease as a
result of redistribution to other organs, which accounts for its short duration of action.
The drug is slowly and completely metabolized in the liver.

Pharmacokinetic Properties

Prep.
and Route
Value Units of Admin. Reference Comments

Absorption
Bioavailability
Distribution
Volume of Distribution 2.5 l/kg Dollery (1999)
Plasma Protein Binding 50–80 % Dollery (1999)
Metabolism
Plasma Half-Life 9 hrs i.v. Dollery (1999)
Bio Half-Life
Clearance 3.4 ml/min/kg i.v. Evers and Crowder (2001)
Routes of Elimination Urine

Targets-Pharmacodynamics

Thiopental potentiates GABAergic neurotransmission through an interaction with the

chloride channel.

Target Name(s):
GABA-A receptors

Therapeutics

Thiopental is used, predominantly, for the induction of general anesthesia. However, as

with all barbiturate drugs, it also has anticonvulsant properties. A single dose maintains
anesthesia for about 5–8 min Evers and Crowder (2001).
 Thiopental 3

Indications

Prep. and Route of

Value Units Admin. Reference Comments

Intravenous anesthesia
Dosage 2.5 % 25 mg/ml isotonic Marshall and Preparation has a pH
solution, i.v. Longnecker (1996) of 10–11.

Contraindications
The only absolute contraindication for thiopental is in individuals with a history of
porphyria.

Adverse Effects
Adverse effects include hypersensitivity reactions, respiratory depression, pain at the site
of injection, accidental intra-arterial injection may result in thrombosis, necrosis and
possibly gangrene.

Pre-Clinical Research
Pharmacokinetics

Potency

Prep. Exp.
Organ/ and Route Cell Line/ End
Value Units Tissue of Admin. Type Effects Point Reference Comments

Mouse
DOSE 25 mg/kg i.v. Anesthesia Merck Index
(2001)
LD50 78 mg/kg i.v. Barnes and
Eltherington
(1965)
LD50 149 mg/kg i.p. Barnes and
Eltherington
(1965)
Rat
DOSE 20 mg/kg i.v. Anesthesia Barnes and
Eltherington
(1965)
DOSE 40 mg/kg i.p. Anesthesia Barnes and
Eltherington
(1965)
LD50 67.5 mg/kg i.v. Barnes and
Eltherington
(1965)
LD50 120 mg/kg i.p. Barnes and
Eltherington
(1965)
Guinea pig
DOSE 20 mg/kg i.v. Anesthesia Barnes and
Eltherington
(1965)
4 Thiopental

DOSE 40 mg/kg i.p. Anesthesia Barnes and

Eltherington
(1965)
Rabbit
DOSE 20 mg/kg i.v. Anesthesia Barnes and
Eltherington
(1965)
Cat
DOSE 28 mg/kg i.v. Anesthesia Barnes and
Eltherington
(1965)
DOSE 60 mg/kg i.p. Anesthesia Barnes and
Eltherington
(1965)

Journal Citations

Lingamaneni, R., Hemmings, H.C., 2003. Differential interaction of anaesthetics and antiepileptic drugs with
neuronal Na+ channels, Ca2+ channels, and GABA(A) receptors. Br. J. Anaesth., 90(2), 199–211.

Book Citations

Marshall, B.E., Longnecker, D.E., 1996. General Anesthetics. Hardman, J.G., Limbird, L.E. (Ed.), Goodman
and Gilman’s The pharmacological basis of therapeutics, pp. 307–330, McGraw-Hill, New York.
Dollery, C., 1999. Dollery, C. (Ed.), Therapeutic drugs, pp. 92–T95, Churchill Livingstone, London.
Barnes, C.D., Eltherington, L.G., 1965. Drug dosage in laboratory animals, pp. 239, Univ. California Press,
Berkeley.
Merck Index, 2001. O’Neill, M.J. (Ed.), The Merck Index, Edition 13, p. 1667, Merck Research Laboratories,
Whitehouse Station.
Evers, A.S., Crowder, C.M., 2001. General anesthetics. Hardman, J.G., Limbird, L.E. (Ed.), Goodman and
Gilman’s The pharmacological basis of therapeutics, Edition 10, pp. 337–365, McGraw-Hill, New York.

Further Reading

Gottesmann, GABA mechanisms and sleep, Neuroscience, 111(2) 2002 231–239.