Dissociative Anesthetics

Dissociative Anesthetics: Angel Dust to Special K to Ketamine Clinics

Our Love Affair with Drugs ◽

10.1093/oso/9780190051464.003.0010 ◽

2020 ◽

Author(s):

Jerrold Winter

Keyword(s):

Cardiac Rhythm ◽

Drugs Of Abuse ◽

Breast Biopsy ◽

Human Subjects ◽

Anesthetic Agents ◽

Dilation And Curettage ◽

Trade Name ◽

Dissociative Anesthetics

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.

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Subunit-dependent Inhibition of Human Neuronal Nicotinic Acetylcholine Receptors and Other Ligand-gated Ion Channels by Dissociative Anesthetics Ketamine and Dizocilpine

Anesthesiology ◽

10.1097/00000542-200004000-00033 ◽

2000 ◽

Vol 92 (4) ◽

pp. 1144-1153 ◽

Cited By ~ 95

Author(s):

Tomohiro Yamakura ◽

Laura E. Chavez-Noriega ◽

R. Adron Harris

Keyword(s):

Ion Channels ◽

Nmda Receptors ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Dependent Manner ◽

Neuronal Nicotinic Acetylcholine Receptors ◽

Glycine Receptors ◽

Nicotinic Acetylcholine ◽

Dissociative Anesthetics ◽

Gated Ion Channels

Unlabelled Background The neuronal mechanisms responsible for dissociative anesthesia remain controversial. N-methyl-D-aspartate (NMDA) receptors are inhibited by ketamine and related drugs at concentrations lower than those required for anesthetic effects. Thus, the authors studied whether ligand-gated ion channels other than NMDA receptors might display a sensitivity to ketamine and dizocilpine that is consistent with concentrations required for anesthesia. Methods Heteromeric human neuronal nicotinic acetylcholine receptors (hnAChR channels alpha2beta2, alpha2beta4, alpha3beta2, alpha3beta4, alpha4beta2 and alpha4beta4), 5-hydroxytryptamine3 (5-HT3), alpha1beta2gamma2S gamma-aminobutyric acid type A (GABAA) and alpha1 glycine receptors were expressed in Xenopus oocytes, and effects of ketamine and dizocilpine were studied using the two-electrode voltage-clamp technique. Results Both ketamine and dizocilpine inhibited hnAChRs in a noncompetitive and voltage-dependent manner. Receptors containing beta1 subunits were more sensitive to ketamine and dizocilpine than those containing beta2 subunits. The inhibitor concentration for half-maximal response (IC50) values for ketamine of hnAChRs composed of beta4 subunits were 9.5-29 microM, whereas those of beta2 subunits were 50-92 microM. Conversely, 5-HT3 receptors were inhibited only by concentrations of ketamine and dizocilpine higher than the anesthetic concentrations. This inhibition was mixed (competitive/noncompetitive). GABAA and glycine receptors were very resistant to dissociative anesthetics. Conclusions Human nAChRs are inhibited by ketamine and dizocilpine at concentrations possibly achieved in vivo during anesthesia in a subunit-dependent manner, with beta subunits being more critical than alpha subunits. Conversely, 5-HT3, GABAA, and glycine receptors were relatively insensitive to dissociative anesthetics.

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DISSOCIATIVE ANESTHETICS DISPLAY DIFFERENTIAL INTERACTIONS WITH MULTIPLE SUBTYPES OF THE SIGMA RECEPTOR

Anesthesiology ◽

10.1097/00000542-199409001-00791 ◽

1994 ◽

Vol 81 (SUPPLEMENT) ◽

pp. A792

Author(s):

A. D. Weissman ◽

A. Stance

Keyword(s):

Sigma Receptor ◽

Dissociative Anesthetics

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To the method of study of preparations that are often used in anesthetic prac-tice for surgical interventions in small animals

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.32718/nvlvet9245 ◽

2018 ◽

Vol 20 (92) ◽

pp. 218-221

Author(s):

N. V. Nazaruk

Keyword(s):

Wound Healing ◽

Muscle Relaxation ◽

Small Animals ◽

Analgesic Action ◽

Review Of The Literature ◽

Medicinal Products ◽

Pharmacological Agents ◽

Surgical Interventions ◽

Animal Safety ◽

Dissociative Anesthetics

A review of the literature on the study of medicines that is often used in anesthetic practice for surgical interventions in small animals is made. A large arsenal of pharmacological agents and the possibility of their use in various combinations now allow the use of a variety of anesthetic methods. The choice of the method of anesthesia should correspond, above all, to the patient, as well as the nature and duration of the planned operation. As a matter of fact, an anesthetic method should be used to ensure maximum animal safety. It is known that in order to provide effective anesthesia you need: sleep, muscle relaxation (relaxation of muscles), analgesia (anesthesia). To ensure of these three requirements, a number of preparations are used: propofol, ketamine (dissociative anesthetics: zoletil-tieletamine hydrochloride, zelozepam hydrochloride), alpha-2 antagonists – xylazine (xylan, sedacil, sedazin, meditin), opioids (fentanyl, morphine, butorphanol). The characteristic of preparations propofol, ketamine, medetomedine, butorphanol is given. In view of the foregoing, we conclude that a large number of medicinal products are used in operative interventions in estheological practice. However, it is important to emphasize that only a combination of the above preparations among ourselves can provide effective anesthesia, which will increase the analgesic action, reduce the toxicity of these preparations and faster wound healing and recovery.

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