Safer Anesthetics Through Stereochemistry

Inhalation agents such as halothane and isoflurane are the mainstay of clinical anesthesia despite the low therapeutic indices common to this class of drugs.42 This narrow safety margin may be attributed to a significant depression of cardiovascular function as well as deleterious effects on respiration, airway reflexes, and temperature. The management of these side effects represents a significant challenge in the patient undergoing anesthesia and may limit surgery in compromised patients....

Volatile Anesthetic Activity At Neuronal nAChRs

In contrast to the voluminous information about volatile anesthetic actions at the m-nAChR, little is known about their effects on n-nAChRs. Although the first n-nAChR subunit (a3) was cloned in 1986,4 there have been few studies on their modulation by volatile anesthetics. This may be due, in part, to the complexity of the native receptor composition. In addition, after many years of searching for examples of direct synaptic transmission in the CNS, it has only recently become clear that...

Fluorescence Spectroscopy

Fluorescence spectroscopy can be used to monitor ligand-protein interactions, providing information about equilibrium binding energetics, kinetics, and dynamic changes in protein structure after complex formation. Fluorophores may be intrinsic to the protein itself and may be incorporated via covalent attachment or simple partitioning. Intrinsic protein fluorescence is principally due to tryptophan residues, when present, but tyrosine73 and phenylalanine74 fluorescence can also be monitored, in...

Info

B Righting reflex is equated here to the rolling response, typically measured by placing animals in a rotating cage. c Unpublished value for SF6 (14.6 1.3 n 10, SD) based on additivity experiments with desflurane. d Estimated by additivity studies with nitrous oxide. b Righting reflex is equated here to the rolling response, typically measured by placing animals in a rotating cage. c Unpublished value for SF6 (14.6 1.3 n 10, SD) based on additivity experiments with desflurane. d Estimated by...

Uds

Action potentials (APs), 196, 202, 216 Adenosine, 155 Adrenal chromaffin cell studies, 164 165 -Adrenoceptor activation, 154 Aequorin luminescence, 168 ffl-Agatoxin IVA, 148, 162 Age and anesthetic susceptibility, 185, 194 Agrin, see Proteins Airway smooth muscle, 161 Albumin, see Bovine serum albumin (BSA) Alcohols, see also Ethanol long-chain, 261 nonanesthetic compound, 15 sodium channels and, 209 susceptibility of mice to, 114-115 tolerant intolerant rats, 283 Alkanes use as anesthetic...

References

Behnke, A.R., Thomson, R.M., and Motley, E.P., The psychologic effects of breathing air at 4 atmospheres pressure, Am. J. Physiol., 112, 554, 1935. 2. Stedman's Medical Dictionary, 23rd edition, Williams & Wilkins, Baltimore, 1978. 3. Eger E.I., II, and Kissin, I., What is general anesthetic action , Anesth. Analg., 77, 408, 1993. 4. Prys-Roberts, C., Anaesthesia A practical or impractical construct , Br. J. Anaesth., 59, 1341, 1987. 5. Quasha, A.L., Eger, E.I., II, and Tinker, J.H.,...

In Vitro Studies

Optically active inhalation agents that exhibit stereoselectivity in vivo represent novel tools to identify potential targets of anesthesia. The utility of these agents goes beyond a potential resolution of the lipid versus protein controversy9 to an examination of the contribution of a particular pathway, subunit, or domain to the process of anesthesia. Thus, the demonstration of a potency difference between the stereoi-somers of an inhalation agent corresponding to the in vivo situation e.g.,...

Localization And Function Of Pmca In The Central Nervous System

The techniques of in situ hybridization, immunocytochemistry, and histochemistry were combined in an effort to provide a coherent picture of PMCA distribution relevant for further pharmacologic, and particularly, anesthetic studies. We initially focused our localization effort on the PMCA1 isoform, as it represents more than 50 of the total PMCA-related activity in the brain. Localization of the PMCA1 isoform mRNAs was evaluated by in situ hybridization. Uridine 5' a-(35S)thio...

Table

The Four Factors Used in This Chapter to Evaluate Anesthetic Criteria and Mechanisms 1. Is there a unique interpretation in terms of Model I 2. Is there a unique interpretation in terms of Model II 3. Is it generally valid among animals 4. Does it have discriminatory power The most striking thing about the structure of general anesthetics is the variety of chemical compounds that produce anesthesia. The inert gases xenon, argon, and krypton are general anesthetics, as are diatomic gases such as...