Pharmacologic effects of CI‐581, a new dissociative anesthetic, in man

Abstract

Pharmacologic actions of CI-581, a chemical derivative of phencyclidine, were determined in 20 volunteers from a prison population. The results indicate that this drug is an effective analgesic and anesthetic agent in doses of 1.0 to 2.0 mg. per kilogram. With intravenous administration the onset of action is within 1 minute and the effects last for about 5 to 10 minutes, depending on dosage level and individual variation. No tachyphylaxis was evident on repeat doses. Respiratory depression was slight and transient. Hypertension, tachycardia, and psychic changes are undesirable characteristics of the drug. Whether these can be modified by preanesthetic medication was not determined in this study. Recovery from analgesia and coma usually took place within 10 minutes, although from electroencephalographic evidence it may be assumed that subiects were not completely normal until after 1 to 2 hours. No evidence of liver 01' kidney toxicity was obtained. CI-581 produces pharmacologic effects similar to those reported for phencyclidine, but of shorter duration. The drug deserves further pharmacologic and clinical trials. It is proposed that the words "dissociative anesthetic" be used to describe the mental state produced by this drug.The remarkable analgesic and anesthetic properties of phencyclidine have stimulated a search for derivatives that would offer the same benefits with less psychotomimetic effects. 3 Recent studies in laboratory animals by McCarthy and co-workers7 indicate that such an agent might be found in CI-581, a chemical derivative of phencycli-dine, with the formula, 2-( o-chlorophenyl)-2-methylamino cyclohexanone HCI (Fig. 1). CI-581 produced immobilization and/or general anesthesia in a variety of animals and in a broad range of dosages. Although this compound is less potent on a milligram per kilogram basis than phencyclidine, its central depressant action is significant with much less central excitatory effects. Moreover, CI-581 has a shorter duration of action which should allow greater controlability in clinical use.

The Effects of Intravenous Anaesthetics on the Cardiovascular System of the Rabbit

“…The similarity in the peripheral effects of althesin and ketamine is interesting in view of their known contrasting effects on the blood pressure of both man and several animal species (Domino et al, 1965;McCarthy, Chen, Kaump & Ensor, 1965;Clarke et al, 19 1). In the conscious rabbit, at the highest doses employed in the present study and at the same time after injection of the agent, ketamine increased (McGrath et al, 1975a) and althesin decreased arterial blood pressure.…”

“…It was of interest to compare the purely peripheral effects of these agents since in clinical use (Domino, Chodoff & Corssen, 1965; Clarke, Montgomery, Dundee & Bovill, 1971;Coleman, Downing, Leary, Moyes & Styles, 1972) and in the conscious rabbit (McGrath et al, 1975a;Mackenzie et al, 1976) they produce contrasting effects, althesin behaving rather like the barbiturates in depressing the cardiovascular system, while ketamine elevates both blood pressure and heart rate.…”

Ketaminas Pooperaciniam Skausmui Gydyti

“…Nustatyta, kad pusė tiriamųjų netekdavo sąmonės suleidus į/v 0,5 mg/kg ketamino, o suleidus į/v 2 mg/kg sukelta koma truko vidutiniškai 10 min. Nepageidaujamas vaisto poveikis pasireiškė maždaug 1 iš 3 tiriamųjų, o pooperacinis delyras buvo minimalus [11][12].…”

“…Nustatyta, kad pusė tiriamųjų netekdavo sąmonės suleidus į/v 0,5 mg/kg ketamino, o suleidus į/v 2 mg/kg sukelta koma truko vidutiniškai 10 min. Nepageidaujamas vaisto poveikis pasireiškė maždaug 1 iš 3 tiriamųjų, o pooperacinis delyras buvo minimalus [11][12].Tolesniuose 1965 m. Guenter Corssen ir Edward F. Domino atliktuose tyrimuose nustatyta, kad CI-581 slopina centrinės nervų sistemos gebėjimą reaguoti į tam tikro stiprumo sensorinius impulsus, tačiau nesukelia pilnavertės jų blokados. Todėl ketamino sukeltai būsenai apibūdinti buvo…”

Endokrine Reaktionen nach S-(+)-Ketamin

“…Charakteristisch für die als "dissoziative Anästhesie" [12] bezeichnete Ketamin-Monoanästhesie sind die relativ gute Analgesie bei nicht vollständig ausgeschaltetem Bewußtsein, das regelmäßige Auftreten von Traumreaktionen sowie die deutlichen Anstiege von Blutdruck und Herzfrequenz und ggf. die dilatierende Wirkung auf die Bronchialmuskulatur.…”