2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and Substance-Related-Disorders

Pigeons trained to discriminate 1.0 mg/kg phencyclidine from saline were used to study the interaction between the stimulus effects of phencyclidine and those of (+)-N-allylnormetazocine [(+) NANM], pentobarbital and d-amphetamine using a cumulative-dosing procedure. Both (+) NANM and pentobarbital enhanced the discriminative stimulus effects of phencyclidine. The enhancement of the phencyclidine stimulus by pentobarbital was predicted by adding the effects of the individual drugs, but the enhancement of the phencyclidine stimulus by (+) NANM was sometimes more than would have been expected from adding the effects of the individual drugs. d-Amphetamine did not enhance the discriminative stimulus effects of phencyclidine, but neither did it interfere with these effects. Combinations of (+) NANM or pentobarbital with phencyclidine also enhanced the rate-decreasing effects of phencyclidine, but to a lesser extent than they enhanced the discriminative stimulus effects of phencyclidine. d-Amphetamine only slightly enhanced the rate-decreasing effects of phencyclidine.

Topics: Amphetamines; Animals; Columbidae; Discrimination Learning; Drug Interactions; Pentobarbital; Phenazocine; Phencyclidine; Substance-Related Disorders

Effects of drugs known to disrupt performance in an 8-arm radial maze are reported in terms of changes caused in the pattern of arm entry. Phencyclidine (PCP) and N-allyl-N-normetazocine (SKF-10,047) alter the pattern of arm entry in a way which distinguishes their actions from those of scopolamine and certain serotonergic agonists. The apparent rank order of potencies for causing this effect is (+)SKF-10,047 greater than PCP greater than (-)SKF-10,047. Results of previous radial maze studies evaluating the interactions of clonidine and verapamil with PCP are summarized. Data are reported which indicate that the ability of verapamil to potentiate PCP's behavioral effects stems from an alteration of the pharmacokinetics of PCP; when verapamil (20 mg/kg, IP) was administered 15 minutes before [3H]PCP (40 microCi/kg, IP), brain levels of tritium were increased by 154 to 225 percent. Finally, possible advantages of using a 4-arm radial maze in studies of PCP and related drugs are discussed.

Topics: Animals; Brain; Learning; Lysergic Acid Diethylamide; Memory; Organ Specificity; Phenazocine; Phencyclidine; Scopolamine; Substance-Related Disorders; Verapamil

Tolerance to the behavioral effects of selected opiate compounds (cyclazocine, ketocyclazocine, naloxone and the stereoisomers of N-allylnormetazocine) and phencyclidine was evaluated using cumulative dosing procedures in rhesus monkeys responding under a fixed-ratio (FR) schedule of food presentation. Initially, the i.v. injection of graded doses of each drug in 8-min time-out periods preceding sequential FR periods decreased responding after each time-out in dose-related fashion. Subsequently, daily administration of up to 11 mg/kg of cyclazocine led to an approximately 16 to 32-fold rightward shift in the dose-effect curves for cyclazocine and ketocyclazocine and an approximately 4-fold rightward shift in the dose-effect curves for phencyclidine and (+)-N-allynormetazocine. In contrast, the dose-effect curves for naloxone and (-)-N-allynormetazocine were generally unchanged or shifted leftward. Termination of daily cyclazocine administration produced signs of withdrawal which disappeared over several days in all monkeys. These included emesis, frequent aggressive display and disruption of schedule-controlled performance. Present results suggest that the rate-decreasing effects of racemic cyclazocine involve mechanisms distinct from those mediating the rate-decreasing effects of naloxone or (-)-N-allynormetazocine. The differing degrees of cross-tolerance produced to the rate-decreasing effects of ketocyclazocine and of phencyclidine and (+)-N-allynormetazocine also suggest that the latter compounds produce behavioral effects to some extent through mechanisms distinct from those through which ketocyclazocine is effective.

Topics: Animals; Behavior, Animal; Cyclazocine; Dose-Response Relationship, Drug; Drug Tolerance; Ethylketocyclazocine; Food; Macaca mulatta; Male; Naloxone; Phenazocine; Phencyclidine; Stereoisomerism; Substance-Related Disorders

Topics: Animals; Binding Sites; Dogs; Guinea Pigs; Humans; Male; Middle Aged; National Institutes of Health (U.S.); Nicotine; Opioid-Related Disorders; Opium; Phenazocine; Saimiri; Self Administration; Substance-Related Disorders; Tobacco Use Disorder; United States

Six female chronic spinal dogs were administered N-allylnormetazocine (NANM) chronically by the intravenous route starting at 0.3 mg/kg/day. The dose was escalated to a stabilization dose of 10 mg/kg/day. The dogs became tolerant to NANM's ability to produce canine delirium and its anorexigenic and respiratory stimulant effects. Naltrexone increased the amplitude of the flexor reflex and pulse rate in the body temperature, pupillary constriction, bradycardia and tachypnea. Appetite was decreased and weight was lost. These data indicate that chronic administration of NANM produces tolerance and a unique type of physical dependence. Some changes produced by chronically administered NANM were naltrexone antagonizable, others were not suggesting that NANM may have several mechanisms of action.

Topics: Animals; Body Temperature; Decerebrate State; Dogs; Drug Tolerance; Eating; Female; Humans; Naltrexone; Phenazocine; Pulse; Pupil; Reflex; Substance-Related Disorders