Dissociative Anesthetics: Angel Dust to Special K to Ketamine Clinics

Phencyclidine (PCP) and ketamine are anesthetic agents with unique pharmacological properties, distinct from depressant drugs, as they produce anesthesia without suppressing breathing. PCP was synthesized in 1956 and tested in animals, showing effects ranging from excitement to quieting and analgesia. Human studies began in 1957 at Detroit Receiving Hospital, first in seven volunteers, then in 64 patients aged 18 to 78 (47 women) undergoing surgeries like breast biopsy and hysterectomy. Intravenous PCP provided profound analgesia, often allowing surgery without additional drugs.

Study at a glance

Abstract

We will consider just two drugs in this chapter. They are phencyclidine and ketamine. Both are widely used as anesthetic agents, ketamine in humans and phencyclidine in animals. The acronym for phencyclidine that we will use, PCP, comes from its chemical name 1-(1-PhenylCyclohexyl)-Piperidine. In addition to their medical use, both ketamine and PCP have gained roles as recreational drugs or, as others would put it, drugs of abuse. While sharing some of the properties of the depressant drugs we met in the preceding chapter, PCP and ketamine are pharmacologically and ther­apeutically unique. On March 26, 1956, V. Harold Maddox, a chemist working at the research laboratories of Parke, Davis & Company in Detroit, synthesized a novel compound later to be called phencyclidine. PCP was submitted in the autumn of that year for testing in animals. Pigeons, mice, rats, Guinea pigs, rabbits, dogs, cats, and monkeys all had their turn. Depending on the dose employed and the species in which it was tested, the effects ranged from excitement and stimulation to taming and quieting. Analgesia, that is, absence of pain without loss of consciousness, and anesthesia were common but, unlike the depressant drugs we met in the previous chapter, the anesthesia was not accompanied by depression of breathing. Studies in human subjects began in May 1957 at the Department of Anesthesiology of the Detroit Receiving Hospital. By this time, PCP had been given the trade name Sernyl. The drug initially was administered to seven volunteers. As had previously been noted in animals, there was no suppression of breathing or disturbance of cardiac rhythm, highly desirable qualities in an anesthetic agent. The investigators then moved on to 64 patients ranging in age from 18 to 78, 47 of whom were women, who were to undergo various surgical procedures, including breast biopsy, dilation and curettage, skin grafts, hysterectomy, and hernia repair. Immediately after the intravenous administration of PCP, there was what the anesthesiologists called “a profound state of analgesia” permitting surgical incision and, in many cases, completion of the operation without the use of other drugs.