Thiobarbital is a barbiturate sedative-hypnotic.
|S. NO.||PHYSICAL AND CHEMICAL PROPERTIES|
|1||Molecular weight||200.26 g/mol|
|4||Octanol/water partition coefficient||LogP = 1.5|
|5||Presence of ring||Pyrimidine|
|6||Number of chiral centers||Not present|
Mechanism of Action
i. Drug binds with different binding sites associated with chloride ionopore at the GABAA
ii. This results in increase in the duration of time for the opening of the chloride ionopore.
iii. As a result, the post synaptic inhibitory effect of GABA in the thalamus is prolonged.
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 barbiturates 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 5th-position substituents yields agents with analgesic activity but with weak hypnotic properties.
- Introduction of the polar functional group at the 5th– 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 2nd-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. 
Method of synthesis
Thiobarbital can be synthesized by reaction of barbital with phosphorous pentasulfide.
Thiobarbital is used for:
- Central nervous system depression
Side effects of Thiobarbital are:
- Respiratory problems
- Lack of coordination
- Memory weakness
Q.1 Thiobarbital potentiates GABA receptors, which results in?
a) Increase in opening duration of chloride ion channels
b) Decrease in opening duration of chloride ion channels
c) Decrease in binding affinity of GABA
d) Both b) and c)
Q.2 Therapeutic use of drug Thiobarbital is/are?
a) CNS depression
b) Arrhythmia treatment
d) All of the above
Q.3 Which amongst the following are the correct statements with respect to the SAR of drug Thiobarbital
I. As the number of carbons at R2 carbon increases, the lipophillicity of the drug decreases
II. Introduction of the polar functional group at the 5th– position yields compounds which are fully devoid of sedative-hypnotic or anticonvulsive activity
III. Esterification of the 5th-position substituents yields agents with analgesic activity and strong hypnotic properties..
IV. Substitution of either of the 1,3-diazine nitrogens with aliphatic carbons retains the anticonvulsive properties..
a) I, III
b) II, IV
c) I, II
d) III, IV
Q.4 The starting chemicals required for the synthesis of drug Thiobarbital?
a) Phosphorous pentasulfide
c) Both a) and b)
d) None of the above
Q.5 Correct sequence for the True/False for the physiochemical properties of the drug thiobarbital is?
I. Molecular weight is 300.2 g/mol
II. It is present form
III. Melting point is 180oC
IV. 1 chiral carbons are present in the structure of barbital.
Q.6 Correct statements for the IUPAC nomenclatures of the drugs are?
I. Thiobarbital: 5,5-diethylpyrimidine-2,4,6(1H,3H,5H)-trione.
II. Amobarbital: 5-ethyl-5-(3-methylbutyl)-1,3-diazinane-2,4,6-trione
III. Thiamylal: 5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione
IV. Phenobarbital : 5-Ethyl-5-phenyl-1,3-diazinane-2,4,6-trione
a) II, III
b) II, IV
c) I, II, IV
d) I, III
Q.7 Match the following drugs with their correct classifications-
|i. Phenylpropanolamine||A. Barbiturate sedative-hypnotic|
|ii. Methyldopa||B. Mixed-acting sympathomimetics|
|iii. Thiobarbital||C. Nonselective adrenergic antagonist|
|iv. Phenoxybenzamine||D. Selective α2-adrenergic agonist|
a) i-A, ii-B, iii-C, iv-D
b) i-B, ii-D, iii-A, iv-C
c) i-A, ii-D, iii-C, iv-B
d) i-C, ii-A, iii-B, iv-D
REFERENCES Lemke TL, Zito SW, Roche VF, Williams DA. Essentials of Foye’s principles of medicinal chemistry. Wolters Kluwer; 2017, 490-91