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W D Paton

Publications and source records attributed to W D Paton.

82 records · Page 5Linked to original sources
PubMed1966

Experiments on the genesis of bubbles as a result of rapid decompression.

1. The time course of intravascular bubble formation in mice after rapid decompression from 150 Lb/sq. in. has been followed in vivo in a flap preparation of thoracic and abdominal skin.2. Gas appeared first in the arteries, moving distally after a latent period of 3 min or more. Then bubbles appeared, moving centrally, in the venous system.3. The arterial bubbles could not be attributed to air forced into the circulation from the lungs or lumen of the gut.

Abdomen↗
PubMedDate not supplied

Species variation and the mechanism of pressure-anaesthetic interactions.

The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be eliminated by pressures of approximately 100 atm (refs 3, 4). However, the effects of anaesthetics are not always reversed in model systems, where there is evidence that the pattern of pressure reversal varies significantly. We now find that pressure fails to reverse the effects of anaesthetics on the freshwater shrimp (Gammarus pulex), although the sensitivity of these crustaceans to anaesthetics is comparable with that of higher animals. This is hard to reconcile with traditional bio-physical mechanisms and indicates that anaesthetics may act at a specific protein site rather than having a general effect on cell membranes. The pharmacology of pressure in mammals seems to be more similar to that of strychnine than of any other central stimulant. As glycine, whose action is blocked by strychnine, is absent as a neurotransmitter in the arthropod central nervous system, we believe that this substance may be involved in determining pressure-anaesthetic interactions in vertebrates.

Anesthesia↗
PubMedDate not supplied

The anesthetic effect of oxygen.

Low pressures of O2 (3 to 5 atm) cause convulsions in mice but higher pressures produce a state very similar to anesthesia. The authors estimated the anesthetic potency of O2 in mice which were exposed to either N2O alone, N2O + NaBr, or O2 + NaBr. From the dose-response curves, ED50S were derived for the gases. The ED50 for N5O alone was 1.50 +/- 0.036 atm (n = 12) and 1.11 +/- 0.041 atm (n = 12) in the presence of NaBr, a reduction of 25 percent. The O2 ED50 with NaBr was 3.91 +/- 0.077 atm (n = 12). After correction for the NaBr, the ED50 of O2 is estimated at 5.3 atm. This is lower than predicted from the lipid solubility of O2.

Anesthesia, Inhalation↗
PubMedDate not supplied

Biotransformation of cannabidiol in mice. Identification of new acid metabolites.

The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid.

Animals↗
PubMedDate not supplied

Pharmacokinetics of delta 9-tetrahydrocannabinol in rabbits following single or multiple intravenous doses.

The pharmacokinetics of delta 9-tetrahydrocannabinol (delta 9-THC) has been studied in rabbits under conditions of single or multiple administration. Measurement of the drug was by a sensitive GC/MS technique using metastable ion monitoring and capable of measuring 0.005 ng/ml of the drug in plasma. This method enabled measurements of the drug to be made for 8-10 days after a single iv dose of 1 mg/kg of delta 9-THC and for 26 days following treatment for 22 days with the same dose. Plasma concentration-time data were analyzed by least squares nonlinear regression with the program NONLIN and terminal half-lives in the range 30-66 hr [mean 47.1 +/- 3.5 (SE), n = 8] were found after acute drug treatment. These increased to 74.6 +/- 1.7 hr (n = 4) after an 8-day treatment and to 83.0 hr after the 22-day treatment. Plasma clearance values were high, but the large amount of drug sequestered in tissues, reflected by large volumes of distribution, was the main determinant of terminal half-life. Measurements of the drug in several tissues indicated that fat was the major site of sequestration. The relative concentrations of delta 9-THC in the various tissues were similar to those observed for other lipophilic compounds, suggesting that distribution of delta 9-THC is governed by its physicochemical properties and not by any active transport process or specific barriers.

Animals↗
PubMedDate not supplied

Identification of in vivo liver metabolites of delta 6-tetrahydrocannabinol produced by the mouse.

Metabolites of delta 6-tetrahydrocannabinol (THC) were extracted from livers, separated from lipids by chromatography on Sephadex LH-20, and identified by combined gas chromatography and mass spectrometry. Three alcohols, delta 6-THD-7-oic acid, five diols, six triols, five monohydroxy acids, six dihydroxy acids, two substituted ketones, an epoxide, three diols produced by hydrolysis of the epoxide, three dihydro metabolites, and a glucuronide conjugate were identified. Several other metabolites were detected but not identified. The metabolites were similar to those produced by delta 1-THC in that allylic and side-chain hydroxylation coupled with carboxylic acid formation at C7 were the major biotransformation pathways. delta 6-THC was found to be metabolized more extensively via the epoxide-diol pathway than the delta 1-isomer.

Alcohols↗
PubMedDate not supplied

Identification of the in vivo liver metabolites of (--)-delta 7-tetrahydrocannabinol produced by the mouse.

The major in vivo metabolites of (--)-delta 7-tetrahydrocannabinol were extracted from the livers of mice after a single intraperitoneal dose and were examined by combined gas-liquid chromatography-mass spectrometry. Twenty-six metabolites were identified; most of these appeared to be produced via epoxidation of the double bond, although the epoxides themselves were not detected. Major metabolites involved hydroxylation of the double bond, to give the isomeric 1 alpha- and 1 beta, 7-dihydroxyhexahydrocannabinols. Of these, the 1 alpha, 7-isomer was the major product and appeared to be produced by hydrolysis of 1 alpha, 7-epoxyhexahydrocannabinol. It was further oxidized to 1 alpha-hydroxyhexahydrocannabinol-7-oic acid. Rearrangement of the epoxide to the 7-aldehyde and subsequent reduction to either the 7-alcohol or oxidation to the 7-acid was another major metabolic route. Derivatives of all these metabolites, hydroxylated in the 2"-, 3"- and 4"-positions of the sidechain were also identified. Allylic hydroxylation, predominantly at position 6, was also observed, but this was a relatively minor route. Reduction of the double bond yielded the isomeric axial and equatorial hexahydrocannabinols in low yield.

Animals↗