Dissociative Anesthetics: Angel Dust to Special K to Ketamine Clinics

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.

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

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.

Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?

Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. Slight clinical differences are observed for each etiology. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. In this review, such theories are discussed and faced with the clinical data. In addition, the nosological aspects of hallucinations and psychosis are addressed. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed.

Synthesis and characterization of phencyclidine and his derivatives

Phencyclidine (PCP) or 1-phenyl-cyclohexylpiperidine is the best known representative drug from the compound class of arylcyclohexylamines. On an account of pharmacological activities it belongs to the family of drugs known as a dissociative anesthetics. In recent years, great attention has been paid to the investigation of the substances that have been abused, including PCP. PCP is the synthetic drug with stimulant and hallucinogens effects (street name ?angel dust?) and it's situated on the Schedule Substances List, in Serbia and worldwide. In the beginning, PCP has been sold in pharmacies as local anesthetic, but very quickly it was pulled from sale because of the unwanted effects on consumer?s health causing psychoactive addiction. Taking into the account that today a great attention has been given to the substances that are subject of abuse, in this paper, biological and pharmacological effect of PCP and it's derivative is described. It is shown that PCP is antagonist of N-methyl-D-aspartate (NMDA) and that it causes antiglutamateric hallucinations. Unlike BTCP which agonist is NMDA receptor and is obtained by modifying the structure of PCP. This paper presents a PCP metabolism and provides an overview of the methods for their identification and quantification in the biological samples. Immunological tests of PCP in the biological samples can provide a quick but wrong result because of the possible interference with the other substances of abuse as opposed to instrumental methods. Based on the presented method and the results it was concluded that the method of choice for the examinations of biological samples for the presence of PCP is gas chromatography in combination with mass spectroscopy.