Hexobarbital

Hexobarbital or hexobarbitone, sold both in acid and sodium salt forms as Citopan, Evipan, and Tobinal, is a barbiturate derivative having hypnotic and sedative effects.

It was used in the 1940s and 1950s as an agent for inducing anesthesia for surgery, as well as a rapid-acting, short-lasting hypnotic for general use, and has a relatively fast onset of effects and short duration of action.

[1] Modern barbiturates (such as Thiopental) have largely supplanted the use of hexobarbital as an anesthetic, as they allow for better control of the depth of anesthesia.

[3] The chemical class of barbiturates are one of the oldest sedative-hypnotic agents known, dating back from the introduction of barbital in the early 20th century.

[4] In Eastern Europe, hexobarbital (and other barbiturates) have been regularly used as drugs by pregnant women attempting suicide.

The FDA has classified them as Pregnancy Category D or C.[5] Some research however, indicate that ingestion of Hexobarbital might cause congenital abnormalities.

HST identifies rodents with high or low intensity of microsomal oxidation, so fast (FM) or slow metabolizers (SM).

Hexobarbital and the isozyme can form an enzyme-substrate-complex through a hydroxylation reaction, which is involved in the metabolism of xenobiotics.

the concentration of hexobarbital also plays a role in oxygenase and oxidase activity of hepatic microsomal cytochrome P450.

[12] The biological effects of hexobarbital depend primarily on its ability to penetrate the central nervous system.

[17] All in all, hexobarbital causes an CNS-depressant effect on the brain by inhibiting the glutamate release and potentiating the GABA-effect.

[19] An intoxication in man with hexobarbital can result in sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing and staggering.

Synthesis of hexobarbital by reacting cyclohex-1-enyl 2-cyanopropanoate with guanidine and sodium ethylate, afterwards another methyl group is added through dimethyl sulfate
Alternative pathway for synthesis of hexobarbital by reacting ethyl 2-cyano-2-(cyclohex-1-enyl)propanoate with N -methylurea.
Molecular structure of S(+) and R(-) enantiomers of hexobarbital
Metabolic pathway of hexobarbital