Rolicyclidine

/LABORATORY ANIMALS: Acute Exposure/ Acute lethal dose effects of the carbonitrile precursors and the parent phenylcyclohexyl derivatives of the piperidine, pyrrolidine and morpholine series were determined in order to predict, with respect to the illicit synthesis of these drugs, how contamination with an intermediate precursor might affect the potential toxic effects of the phencyclidine analogue. These studies were conducted in male Swiss Webster mice two weeks after they had been previously used in the rotarod study. Drugs were administered by ip injection and 4 hour LD50s ... were determind using the method of Litchfield and Wilcoxon. Ten mice were used for each dose. Each of the precursors was shown to be more toxic than the parent compound. Using doses expressed as pmole/kg the following potencies relative to the parent derivative were calculated: PCC 1.83 X PCP; PYCC 1.27 X PCPY; and MCC 7.88 X PCM. Within this group of three precursors, their potencies were almost-equivalent: PCC (1.00) - PYCC (.95) > MCC (.80). Among the other derivatives the relationship of their potencies to PCP as determined from the lethal dose studies was as follows: PCPY (1.37) + PCE (1.27) > PCP (1.00) > KET (0.22) > PCM (.19).

/LABORATORY ANIMALS: Neurotoxicity/ Male Swiss Webster mice were tested for their ability to remain on the rod rotating at 5 RPM for a 120 second trial. Following two control trials, each mouse was given an intraperitoneal injection and was tossed at 6 minute intervals for 1 hour after injection. Ten mice were used for each dose. Relative potencies were determined from bioassays using peak effect values and with doses expressed as pmole/kg. The following drugs were employed: (1-phenylcyclohexyl) piperidine HCL (phencyclidine, PCP) 1-[1-(2-thienyl) cyclohexyl] piperidine HCL (TCP) 1-piperidinocyclohexanecarbonitrile free base (PCC) 1-[1-phenylcyclohexyl] pyrrolidine HCL (PCPY) 1-[1-(2-thienyl) cyclohexyl] pyrrolidine HCL (TCPY) 1-pyrrolidinocyclohexanecarbonitrile HCL (PYCC) 1-[1-phenylcyclohexyl] morpholine HCL (PCM) 1-[1-(2-thienyl) cyclohexyl] morpholine HCL (TCM) 1-morpholinocyclohexanecarbonitrile HCL (MCC) N-ethyl-1-1-phenylocyclohohexylamine HCL (PCE) N,N-diethyl-1-phenylcyclohexylamine (PCDEA) N-(n-propyl)-1-phenylcyclohexylamine HCL (NPPCA) 2-(o-chlorophenyl)-2-(methylamine) cyclohexanone (ketamine, KET). The first compounds studied were the cyclohexylpiperidines which included PCP. Setting the potency of PCP equal to 100, it was found that its precursor PCC was only 0.31 times as potent than PCP. A comparison of the cyclohexylpyrrolidines, again letting the potency of PCP equal to 1.00, showed that PCPY was 1.08 times more potent and TCPY 1.54 times more potent. The precursor for this series PYCC was the least potent having a ratio of 0.22.The cyclohexylmorpholine derivatives and precursors were equal to each other in potency although they were only one-fifth as potent as PCP. ... The most potent series of compounds investigated was the amine-substituted phenylcyclohexylamines. Compared to PCP, their relative potencies were 2.15 for PCE, 1.52 for PCDEA and 0.82 for NPPCA...

/LABORATORY ANIMALS: Neurotoxicity/ The discriminative stimulus properties of phencyclidine were evaluated in rats using a two-choice, discrete trial avoidance task in which rats were injected ip with either saline or phencyclidine 1.0 or 3.0 mg/kg 30 minutes prior to the start of the session. Rats were trained until their performance on the appropriate level was 95% correct for 10 consecutive sessions. It was found that rats discriminate PCP from saline in a dose-related manner but the slope in rats trained to the 3.0 mg dose was steeper. In order to further evaluate the discriminative stimulus properties of PCP, a number of PCP analogs were tested. ... The phenyl derivative, 1-[1-phenylcyclohexyl] pyrrolidine HCL (PCPY) was approximately equipotent to PCP in producing PCP-like discriminative stimuli. In addition, the thienyl 67 derivative (PCPY) is equipotent to PCP and PCPY in producing PCF-like discriminative stimuli. ... PYCC also failed to produce any PCP-appropriate responding at non-toxic doses.

/LABORATORY ANIMALS: Neurotoxicity/ Phencyclidine (1-(1-phenylcyclohexyl)piperidine, PCP) self-administration has been demonstrated in rhesus monkeys, baboons, dogs and rats. Generally, an orderly inverted U-shaped dose-response curve for rates of self-injection has been observed. Total drug intake appears to increase slightly with increases in unit dose; however, this increase is much less than might be expected with other CNS depressants such as barbiturates or morphine. Additionally, several arylcyclohexylamine analogues of PCP and some members of the benzomorphan and dioxolane classes referred to collectively as "phencyclinoids" are self-administered by primates and dogs. New data are presented in this review profiling the self-administration of some of these drugs in rats, as well as a characterization of the self-administration of higher unit doses of PCP than previously reported. Also, preliminary results of the assessment of the reinforcing efficacy of some PCP analogues measured by the progressive ratio procedure are presented. /Phencyclinoids/

For more Non-Human Toxicity Excerpts (Complete) data for ROLICYCLIDINE (9 total), please visit the HSDB record page.

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Incapacitating Agents/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations it necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . Demonstrate a friendly attitude and use firm restraint when necessary. All dangerous objects must be removed from the area and anything likely to be swallowed should be kept away from patients, because bizarre delusions may occur. For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Use rapid cooling techniques to manage hyperthermia ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Incapacitating Agents/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures or sedate ... with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Incapacitating Agents/

A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP), which was verified by identification of PHP in the urine. Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms.

Twenty white males who presented with psychosis were later found to have ingested phenylcyclohexylpyrrolidine (PHP). Treatment with haloperidol 5 mg IM caused significant improvement while placebo treatment did not. Results of haloperidol treatment of PHP psychosis were similar to previously published reports with phencyclidine (PCP) psychosis.