Pentobarbital

IUPAC nomenclature

5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione

Classification

Pentobarbital is a barbiturate sedative-hypnotic.

Physiochemical Properties

Mechanism of Action

• Pentobarbital increases the duration of time for which the chloride ionopore is open through binding with GABA_A
• The post-synaptic inhibitory effect of thalamus prolongs.
• There is decreases in GABA sensitive neuronal calcium conductance.
• The overall result is acute potentiation of inhibitory GABAnergic tone.
• Drug also inhibits excitoryAMPA-type glutamate receptors which results in profound suppression of glutamatergic neurotransmission.

Structure Activity Relationship

• Tri-keto form is most stable in aqueous solution.
• 4,6-dialcoholic tautomeric forms are least stable in aqueous solution.
• 5,5-disubstituted barbituric acid is the prime requirement for the barbituares to be sedative hypnotics.
• Esterification of either of the 1,3-diazine nitrogens decreases hypnotic activity.
• Substitution of either of the 1,3-diazine nitrogens with aliphatic carbons retains the anticonvulsive properties.
• Esterification of the 5^th-position substituents yields agents with analgesic activity but with weak hypnotic properties.
• Introduction of the polar functional group at the 5^th– position yields compounds which are fully devoid of sedative-hypnotic or anticonvulsive activity.
• As the number of carbons at R₂ carbon increases, the lipophillicity of the drug increases.
• Modification of the 2^nd-position oxygen of the barbiturate backbone with sulfur atom yields thiobarbiturate derivatives with increased lipophillicity, shorter duration of action, faster time of onset compared to oxy-derivative. [1]

Method of synthesis

i. Diethyl malonate reacts with sodium ethoxide followed by reaction with ethylbromide to give diethyl 2-ethylmalonate.

ii. The compound undergoes reaction with 2-bromopentane.

iii. The above formed compound on reaction with urea yields pentobarbital. [2]

Therapeutic Uses

Pentobarbital is used for:

• Treatment of insomnia
• Sedative before surgery
• Emergency Treatment of seizures

Side Effects

Side effects of Pentobarbital are:

• Insomnia
• Dizziness
• Drowsiness
• Loss of coordination
• Nausea
• Vomiting
• Constipation
• Nightmares
• Restlessness

MCQs 

Q.1 Correct statements related with the physicochemical properties of drug Pentobarbital?

I. Molecular weight = 226.27 gm/mol

II. Physical appearance: red-brown crystalline powder

III. Melting point: 402.5K

IV. Triazole ring present 

a) I, III

b) II, IV

c) I, II

d) I, II, IV

Q.2 Match the following of the drugs with their correct IUPAC names.

a) i-B, ii-C, iii-A, iv-D

b) i-A, ii-C, iii-B, iv-D

c) i-D, ii-A, iii-C, iv-B

d) i-B, ii-D, iii-C, iv-A

Q.3 Correct steps for the mechanism of action of the drug Pentobarbital?

I. Binds with GABA_A receptors

II. Increase in GABA affinity for GABA receptors

III. Opening of chloride channel

IV. Hyperpolarisation

a) I – II – III – IV

b) II – I – III – IV

c) III – I – II – IV

d) II – IV – III – I

Q.4 Correct sequence for True/false for the classification of the drug can be?

• Pentobarbital: benzodiazepine sedative-hypnotic
• Quetipine : benzodiazepine sedative-hypnotic
• Flurazepam: benzodiazepine
• Eszopiclone: butyrophenone

a) TFTF

b) FFTF

c) TFFF

d) FTFT

Q.5 Triketo form of pentobarbital is?

a) Most stable in aqueous solution

b) Least stable in aqueous solution

c) Most soluble in organic solvent

d) Least soluble in organic solvent

Q.6 The correct sequence for the steps for synthesis of drug pentobarbital from diethyl malanoate is?

I. Reaction with 2-bromopentane

II. Reaction with sodium ethoxide

III. Condensation with urea.

a) III – I – II

b) I – II – III

c) I – III – II

d) II – I – III 

Q.7 Side effect of drug Pentbarbital?

a) Insomnia

b) Loss of coordination

c) Nightmares

d) All of the above

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ANSWERS

1-a

2-b

3-a

4-c

5-a

6-d

7-d

REFERENCES