Secobarbital metabolism

Scorch query, database. 56 Sebairol. See Ruuimidc Secobarbital, metabolism of. 76.77.81 Secobaibilat sodium. 494t. 495 Seconal. See Secobarbital sodium Secondary mass spectrometry. 52 Second messengers. 171. 172. 552 Secretin. 854 Seciral. See Acebuiolol Sedatives. See Anxiolytics, hypnotics, and sedatives... 

Unsaturated aliphatic compounds and heterocyclic compounds may also be metabolized via epoxide intermediates as shown in Figure 4.6 and chapter 5, Figure 14. Note that when the epoxide ring opens, the chlorine atom shifts to the adjacent carbon atom (Fig. 4.6). In the case of the furan ipomeanol and vinyl chloride, the epoxide intermediate is thought to be responsible for the toxicity (see below and chap. 7). Other examples of unsaturated aliphatic compounds, which may be toxic and are metabolized via epoxides, are diethylstilboestrol, allylisopropyl acetamide, which destroys cytochrome P-450, sedormid, and secobarbital. 

Chloramphenicol and secobarbital exhibit properties similar to those of tienilic acid, but they have not been studied in humans (11). Oxidative dechlorination of chloramphenicol with formation of reactive acyl chlorides appears to be an important metabolic pathway for irreversible inhibition of CYP. Chloramphenicol binds to CYP, and subsequent substrate hydroxylation and product release are not impaired. The inhibition of CYP oxidation and the inhibition of endogenous NADPH oxidase activity suggest that some modification of the CYP has taken place, which inhibits its ability to accept electrons from the CYP reductase (11). Secobarbital completely inactivates rat CYP2B1 functionally, with partial loss of the heme chromophore. Isolation of the N-alkylated secobarbital heme adduct and the modified CYP2B1 protein revealed that the metabolite partitioned between heme N-alkylation, CYP2B1 protein modification, and epoxidation. A small fraction of the prosthetic heme modifies the protein and contributes to the CYP2B1 inactivation (12). 

Another group of barbiturates is more rapidly metabolized by the liver. Their effects last six or seven hours, and they are called short-acting. They include amobarbital (Amytal), pentobarbital (Nembutal), hexobarbital (Sombulex), and secobarbital (Seconal). These drugs behave very much like alcohol, giving pleasant feelings in low doses, especially as they begin to take effect. There fore, some people seek them out to change the way they feel, and... 

Numerous barbiturates and oral hypoglycemic sulfonyl-ureas also have aliphatic side chains that arc su.sceptible to oxidation. Note that the sedative hypnotic amobarbital (Amytal) undergoes extensive to - I oxidation to the corresponding 3 -hydroxylated metabolite.Other barbiturates, such as pentobarbital, thiamylal,and secobarbital," reportedly are metabolized by way of a and to - I oxidation. The ri-propyl side chain attached to the oral hypoglycemic agent chlorpropamide (Diabinc.se) undergoes extensive to -I hydroxylation to yield the secondary alcohol 2 -hydroxy-chlorpropamide as a major urinary metabolite in humans. " ... 

Barbiturates that have substituents in the 5 position promoting mure rapid metabolism (e.g.. by increasing the lipid/ water partition coefficient) than the intermediate group in-dude Pentobarbital-Sodiunit USP, sodium S-ethyl-S-( I methylbutyDbarbiturate (Nembutal) Secobarbital, IJSP, S-illyl-S-(l-melhylbutyl)barbiluric acid (Seconal) and the sodium salt sodium secobarbital. 

Mechanism-based irreversible inhibition occurs when a reactive metabolic intermediate is formed in situ that can (1) bind covalently with the prosthetic heme through N-alkyllary-lation (e.g., secobarbital), f"2 alkylate the apo-cytochrome (e.g., chloramphenicol or 2-ethy-nylnaphthalene), or (5) cause destruction of the prosthetic heme to products that irreversibly bind to the apocytochrome (e.g. CCI4) (158). These mechanism-based inactivators have primarily been designed and used for the selective inhibition of specific CYP enzymes and elucidating the mechanism of P450 reactions. Some drugs (e.g., aromatase inhibitors)... 

Feuer DJ, Wilson WR, Ambre JJ. Duration of effect of secobarbital on the anticoagulant effect and metabolism of warfarin. Pharmacologist (1974) 16,195. 

Barbiturates such as pentobarbital, amobarlntal and secobarbital and other compounds such as tolbutamide and p-nitrotoluene undergo metabolic hydroxylation to the corresponding alcohols. 

Figure 7.13 Some additional examples of a-oxidations. Top secobarbital is metabolized to a secondary (allylic) alcohol. Bottom a major site of metabolism of the NSAID celecoxib is the aromatic methyl group to give a primary alcohol. This is usually subject to further oxidative metabolism.

Compounds containing an allyl group are susceptible to either olefinic or allylic oxidation (Figs 4.10, 4.11). Olefinic oxidation is mediated with an epoxidation step like the metabolism of secobarbital to secodiol. Allylic oxidation does not produce epoxide intermediates. The generated alcohol is conjugated with glucuronic add in phase II metabolism in order to increase the compound hydrophUi-dty and consequently the urinary excretion. An example of... 

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