Frieda G. Rudo

The Fluorinated Anesthetics

Certain hydrocarbons such as ethylene and cyclopropane elicit surgical anesthesia when inhaled in sufficient concentrations. The saturated hydrocarbons of the aliphatic series do not evoke anesthesia. Anesthetic properties are conferred upon the lower members of this series of hydrocarbons by halogenation with either chlorine or bromine For example, chloroform and ethyl chloride have been used as anesthetics for more than a century. It therefore appeared prudent to determine the effect of halogenation of hydrocarbons and ethers with fluorine in order to determine what effect the presence of fluorine in the molecule would exert on the anesthetic properties of these compounds. The wisdom of this effort has been justified by the investigations of the last two decades, leading to the production of the most useful anesthetic agents containing fluorine. This chapter portrays this signal advance in the field of anesthesiology.

Antinociceptive activity of pentamorphone, a 14-beta-aminomorphinone derivative, compared to fentanyl and morphine.

The analgesic potency of pentamorphone, a 14-β-aminomor-phinone derivative, was compared to that of fentanyl and morphine by examining quantal dose-effect curves generated from data obtained in the mouse hot plate, rabbit tooth-pulp, and dog tail clamp tests. Onset and duration of antinociceptive effects were also compared. The ED50 values (mg/kg) were determined in mice for pentamorphone (0.0039), fentanyl (0.016), and morphine (7.3). In the rabbit tooth pulp test the ED50 values were 0.0009 mg/kg for pentamorphone, 0.0074 mg/kg for fentanyl, and 1.1 mg/kg for morphine; in the dog tail clamp test these values were 0.012 mg/kg for pentamorphone and 0.018 mg/kg for fentanyl. Duration of action (defined as the time until response to tooth pulp stimulation declined to 50% of maximum possible effect [MPEI) was 10 min with twice the IV ED50 for pentamorphone in mice. This duration was similar to that of the equipotent dose of fentanyl but much shorter than the duration of an equipotent potent dose of morphine (60 mid. The duration in rabbits of the ED98 (IV) dose of pentamorphone was 65 min compared to 35 min for an equipotent dose of fentanyl and 200 min for morphine. Intramuscular doses of pentamorphone had significantly faster onset and shorter duration times than equipotent doses of morphine in both mice and rabbits. Pretreatment with naloxone in mice and rabbits attenuated the development of the antinociceptive effects of pentamorphone. This study shows that pentamorphone is a potent analgesic with a duration of action similar to that of fentanyl.

Anesthesia LXXI. Pharmacologic and Physicochemical Comparison of Flurothyl and Its Isomer.

Discussion and summary The pharmaco-logic antagonism between the isomers is striking. It appears that each isomer is competing for its respective receptor site, namely, the convulsive or anesthetic site. In the “balanced state” the action of one is nullified by the other, and an apparently normal animal results. Not any of the physicochemical properties or measurements conducted on the isomers, flurothyl and ISO, revealed a marked difference which might be considered responsible for their respective pharmacologic responses. The surfactant phenomenon was not a constant finding with all fluorinated, convulsive ethers. We were unable to establish any relationship between this physical property and pharmacologic response; however, it was sufficiently unusual and interesting to warrant exploration.

The anesthetic properties of 1, 1,-difluoro-2, 2, 2-trichloroethyl methyl ether.

INCE Robbins’ comprehensive study1 on S fluorinated hydrocarbons and ethers as anesthetics, in 1946, activity in this field has been intensive. These studies have yielded such clinically useful compounds as fluroxene, halothane, and methoxyflurane. In our search for new and better anesthetic compounds, I,l-difluoro-2,2,2-trichloroethyl methyl ether (TCMF) showed promise as an anesthetic in the preliminary screening.

Nitrites. XVII. Tetrahydroxyethylethylenediamine tetranitrate as a coronary artery dilator.

Abstract A new organic nitrate THEN has been studied pharmacologically and shown to be a coronary artery dilator that is tantamount in its activity to that of glyceryl trinitrate. The compound is effective upon oral administration and our animal studies indicate that the agent might serve effectively in the prophylactic treatment of angiospastic disease.