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R C Terrell

Publications and source records attributed to R C Terrell.

11 recordsLinked to original sources
PubMed1998

Rat strain minimally influences anesthetic and convulsant requirements of inhaled compounds in rats.

UNLABELLED: We assessed the effect of rat strain on susceptibility to anesthesia and convulsions produced by inhaled compounds. We determined the minimum alveolar anesthetic concentration (MAC) of desflurane and nitrous oxide, and the convulsive 50% effective dose (ED50) of 1,2-dichlorohexafluorocyclobutane, flurothyl, and difluoromethyl-1-chlorotetrafluoroethyl ether in five strains (three inbred [Long Evans, Sprague-Dawley, and Wistar] and two outbred [Fischer and Brown Norway]). Strain had slight effects on anesthetic potency, the strains with the highest MAC values (Long Evans and Brown Norway) having values < or =28% greater than the strains with the lowest values (Sprague Dawley and Wistar). MAC for nitrous oxide correlated directly with MAC for desflurane as a function of strain. MAC for either desflurane or nitrous oxide correlated inversely with the convulsive ED50 of 1,2-dichlorohexafluorocyclobutane, but correlated poorly (and directly) with the convulsive ED50 of the remaining compounds. Convulsivity varied little as a function of strain (greatest difference 21%) and did not vary consistently as a function of strain. No consistent difference was seen between inbred versus outbred strains. IMPLICATIONS: Rat strain has a minimal effect on the potency of inhaled anesthetics or the convulsant activity of inhaled compounds. It seems that the sites acted on by inhaled compounds to produce anesthesia and convulsions are conserved across common rat strains.

Anesthesia↗
PubMed1989

Halogenation and anesthetic potency.

Previous studies have shown that the anesthetic potency of organic compounds increases as a given halogen is replaced with successively larger halogens. These studies often are limited in the accuracy of determination of potency, rarely correlate potency with physical properties, and usually fail to include ether compounds. Because establishing relationships between structure and activity may shed light on anesthetic action, we studied the new anesthetic, I-537 (CHF2-O-CHBr-CF3), relative to two other ether anesthetics, I-653 (CHF2-O-CHF-CF3) and isoflurane (CHF2-O-CHCl-CF3) for both of which MAC and oil/gas partition coefficients are accurately known. The oil/gas partition coefficient of I-537 at 37 degrees C was found to be 245 +/- 6 (mean +/- SD) and the MAC in Sprague-Dawley rats 0.52 +/- 0.07%. Increasing atomic weight of the 1-ethyl halogen (i.e., F in I-653, Cl in isoflurane, and Br in I-537) progressively decreases MAC (increases potency) and increases lipid solubility. Although potency and solubility change by more than 10-fold, the product of MAC and the oil/gas partition coefficient remains essentially constant (120 +/- 11). However, this product is significantly less than that for other inhaled anesthetics, a finding which either challenges the unitary theory of narcosis or suggests that the lipid solvent classically used to model the site of anesthetic action (olive oil) is inappropriate.

Anesthetics↗
PubMed1988

MAC of I-653 in beagle dogs and New Zealand white rabbits.

The minimum alveolar concentration (MAC) of I-653 was determined in six beagle dogs and four New Zealand white rabbits. The MAC values (+/- SD) were 7.2 +/- 1.0 atm % for dogs and 8.9 +/- 0.3 atm % for rabbits. Comparison of these results with published MAC values for other anesthetics indicate that I-653 is one-third to one-eighth as potent as currently available volatile anesthetics (enflurane, isoflurane, and halothane). From these data and previous reports, human MAC was projected to be approximately 5.1 atm %.

Anesthesia, Inhalation↗
PubMed1984

Physical and chemical properties of anaesthetic agents (with an appendix on the manufacture of isoflurane).

The physical and chemical requirements of today's modern inhalation anaesthetic agents have resulted in the production of compounds that closely approach those of the ideal agent. As medical science develops and defines the need for better drug characteristics, the complexity of the research problems for the organic chemist is intensified. Many of the inhalation anaesthetic agents in use 30 yr ago would not pass a clinical investigator screen today, and would be rejected as inhalation anaesthetic agents. An outline of the manufacture of isoflurane is given as an Appendix to this paper.

Anesthesia, Inhalation↗
PubMed1981

Minimum alveolar concentrations and oil/gas partition coefficients of four anesthetic isomers.

We determined the minimum alveolar concentration (MAC) of four structural isomers having the empirical formula C3H2F5CIO in dogs. MAC for three of the four isomers (including isoflurane and enflurane) ranged from 1.41 to 2.67 (volumes per cent at one atmosphere pressure). The olive oil/gas partition coefficients at 37 degrees C for these isomers ranged from 90.8 to 96.6. In contrast, MAC for the fourth isomer, compound 485, was 12.53 per cent atm. However, the oil/gas partition coefficient for that compound was 25.8. These results suggest that isomer 485, despite its high MAC, does not deviate strikingly from the established correlation between anesthetic potency and lipid solubility.

Anesthetics↗
PubMed1981

Are convulsant gases also anesthetics?

This study investigated whether the convulsant gas flurothyl deviates from the correlation between anesthetic potency and lipid solubility. Flurothyl (CF3CH2OCH2CF3) produced convulsions in 50% of mice at 0.122 +/- 0.006% atm. Mice often convulsed repeatedly after exposure to flurothyl, the maximum number of convulsions occurring when the concentration was 0.24% atm. Concentrations greater than 0.6% atm produced convulsions immediately after addition of flurothyl, but rarely at later times. An ED50 value for loss of the righting reflex was obtained when the concentration was 1.22 +/- 0.19% atm. The oil/gas partition coefficient was found to be 46.9 for flurothyl at 37 C. The product of righting-reflex ED50 and oil/gas partition coefficient (0.0122 atm x 46.9 = 0.57 atm) is similar to that found for conventional anaesthetics in mice. Therefore, flurothyl does not deviate from the correlation of anesthetic potency and lipid solubility. It was also found that 0.3 to 0.8% atm flurothyl increased isoflurane MAC in dogs, but that 3 to 4% atm flurothyl decreased it. The increase of isoflurane requirement at lower concentrations of flurothyl suggests that anesthetics with a potential to cause convulsions may partly antagonize their own anesthetic effect. The decrease in isoflurane MAC in dogs at higher concentrations of flurothyl also implies that this compound has an anesthetic effect. A structural isomer of flurothyl, iso-Indoklon [(CSF3)2CHOCH3], was only anesthetic and did not have convulsant properties. Its MAC in dogs was 4.60 +/- 0.45% atm, and its righting-reflex ED50 in mice was 2.65 +/- 0.13% atm. The product of iso-Indoklon MAC in dogs and its oil/gas partition coefficient (27.0) was 1.24 atm, and the product of iso-Indoklon righting-reflex ED50 in mice and oil/gas partition coefficient was 0.72 atm. These values are close to those found for conventional anesthetic agents in dogs and mice; thus iso-Indoklon also does not deviate from the correlation between anesthetic potency and lipid solubilities.

Anesthesia, Inhalation↗
PubMedDate not supplied

Some characteristics of an exceptionally potent inhaled anesthetic: thiomethoxyflurane.

The authors sought to test whether a deviation existed for the correlation between anesthetic potency and the oil/gas partition coefficient at an extreme of lipid solubility. For thiomethoxyflurane, the sulfur analog of methoxyflurane, the oil/gas partition coefficient was 7230 +/- 50 SEM, and MAC (minimum alveolar concentration of thiomethoxyflurane required for anesthesia) in 4 dogs was 0.035 +/- 0.008 percent of 1 atm. This agrees with the potency predicted by the lipid solubility, although thiomethoxyflurane is 7 1/2 times more potent than methoxyflurane, to date the most potent available anesthetic. Thiomethoxyflurane water/gas and blood/gas partition coefficients were 5.4 +/- 0.3 and 68.1 +/- 1.5, respectively. The latter coefficient accords with the prolonged recovery associated with this agent. Renal and hepatic blood chemistries measured on the 1st and 7th days following anesthesia showed only small changes from preanesthetic values.

Anesthesia, Inhalation↗