Thiopental binding to human serum albumin in the presence of halothane

Albumin binding for the enantiomers of four closely related N-methyl-5-phenyl-5-alkyl-barbiturates 1-4 was investigated for three different mammalian species by means of equilibrium dialysis. Lipid solubility (n-heptane/phosphate buffer distribution coefficient) increased stepwise by a factor of 56 from 1 to 4. Bovine serum albumin: The (S)-(+)-enantiomers of 1-4 were bound in a higher percentage than the (R)-(-)-enantiomers; lengthening of the aliphatic side-chain increased the binding extent in both enantiomeric groups. Human serum albumin: Binding of (S)-(+)-1 and (S)-(+)-4 was higher than that of the (R)-(-)-enantiomers; with (S)-(+)-2 and (S)-(+)-3 it was much lower than that of the corresponding (R)-(-)-enantiomers. Lengthening of the aliphatic side chain increased the binding extent of the (S)-(+)- as well as the (R)-(-)-enantiomers, but with two exceptions: 1. The (S)-(+)-1 binding exceeded that of the (S)-(+)-2 by a factor of nearly two. 2. The binding extent of (R)-(-)-4 was not further increased in comparison to (R)-(-)-3. Rat serum albumin: (S)-(+)-1 and (S)-(+)-2 were bound in a lower percentage than the (R)-(-)-enantiomers, both 3-enantiomers showing an equal binding extent; (S)-(+)-4 was bound to a slightly greater extent than the (R)-(-)-4. In the group of the (S)-(+)-enantiomers, the binding extent increased from 1 to 4, whereas in that of the (R)-(-)-enantiomers only between 1 and 4. Structural differences between the serum albumins of three mammalian species possibly cause the enantioselective binding pattern found for the enantiomers of 1-4, and are responsible for the finding that the binding extent in some cases did not correlate with the lipid solubility of the compounds.

show abstract

Stereoselective Binding of the Enantiomers of Four Closely Related N‐Methyl‐Barbiturates to Human, Bovine, and Rat Serum Albumin

Büch

Krug

Knabe

1996

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

Influence of halothane anaesthesia on protein binding of drugs

Calvo

Súárez

Aguilera

et al. 1994

Eur J Clin Pharmacol

View full text Add to dashboard Cite

We have read the recent report by Vorun et al.[1] "Variation in the binding affinity of warfarin and phenprocoumon to human serum albumin in relation to surgery". They found that the binding affinity of warfarin was reduced in serum samples taken during three days after surgery, Although during surgery the serum concentrations of fatty acid (NEFA) increased markedly, the effect on the binding affinity of oral anticoagulants was surprisingly small. None of the patients was given drugs that could have affected the protein binding of warfarin. Therefore, the influence of a competing ligand was not taken into consideration. However, drugs used during surgery were not considered.We have shown that anaesthetic agents can alter the protein binding of warfarin [2]. In patients undergoing cholecystectomy, we found an increase in the percentage of unbound warfarin 24 h after halothane anaesthesia. Even after 48 h, the percentage of unbound warfarin was still higher than control. Thus, our results are similar to those of Vorun et al. Halothane is metabolished in vivo to trifluoroacetic acid, which can displace drugs from binding sites on serum albumin. Concentrations of trifluoroacetic acid ranging from 0.8 to 2.6 mmol-1-1 have been found in serum from patients 24 h after halothane anaesthesia [3]. The effect of halothane anaesthesia on the protein binding of benzodiazepines [4] and thiopental [5] has also been described.We often forget the possible participation of volatile agents in drug interactions because they are quickly eliminated by the lungs. Binding of warfarin is an important determinant of dose requirement and adverse effects, and we think that the study of Vorun et al. is interesting; however, we suggest that they should give more specific information about anaesthetic drugs.

show abstract

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

McDonagh

Lightner

1992

Experientia

View full text Add to dashboard Cite

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Thiopental binding to human serum albumin in the presence of halothane

Cited by 7 publications

References 11 publications

Stereoselective Binding of the Enantiomers of Four Closely Related N‐Methyl‐Barbiturates to Human, Bovine, and Rat Serum Albumin

Stereoselective Binding of the Enantiomers of Four Closely Related N‐Methyl‐Barbiturates to Human, Bovine, and Rat Serum Albumin

Influence of halothane anaesthesia on protein binding of drugs

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

Contact Info

Product

Resources

About