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Biomedical subjects

A H Tang

Publications and source records attributed to A H Tang.

At least 55 records · Page 3Linked to original sources
PubMed1984

Phencyclidine-like behavioral effects of 2-methyl-3,3-diphenyl-3-propanolamine (2-MDP).

2-Methyl-3,3-diphenyl-3-propanolamine (2-MDP) produced effects in animals similar to those produced by the dissociative anesthetics such as phencyclidine (PCP). Specifically, it shared the discriminative stimulus properties of PCP in rats trained to discriminate PCP (1 mg/kg) from saline; at higher doses, it disrupted brightness discrimination and stimulated locomotor activities in rats trained to avoid shocks in an automated Y-maze; and it produced surgical anesthesia when injected IV to rhesus monkeys. These pharmacological activities were observed only with the levo-isomer of 2-MDP. The dextro-isomer was either inactive or produced opposite effects, depending on the tests. Among several related diphenylpropylamines, 2-MDP represents the optimal structure for potency of PCP-like effects since changes in the amino, 2-methyl and 3-hydroxy groups reduced the potencies of the PCP-like discriminative properties.

Anesthesia↗
PubMed1983

Acquisition of brightness discrimination in the rat is impaired by opiates with psychotomimetic properties.

The acquisition of shock avoidance behavior by rats was studied in an automated Y-maze which incorporates a simultaneous brightness discrimination paradigm. When administered prior to each of 5 consecutive daily sessions, two opiate derivatives with psychotomimetic properties, cyclazocine and N-allylnormetazocine, impaired the acquisition of brightness discrimination at doses which also increased movements between trials. These effects were similar to those produced by phencyclidine, ketamine, and a high dose of d-amphetamine. Pretreatment with morphine, pentazocine and scopolamine at motor stimulant doses before each training session did not affect acquisition of brightness discrimination. Nalorphine, naltrexone, and chlorpromazine also had no effect on brightness discrimination, even at motor depressant doses. Whereas the motor stimulation produced by morphine or pentazocine was blocked by naltrexone, the motor stimulation and discrimination disruption produced by cyclazocine or N-allylnormetazocine were only incompletely antagonized by naltrexone. The results demonstrate similarities between psychotomimetic opiates and phencyclidine-like compounds and may reflect the sensory or cognitive disturbance produced by these drugs in man.

Animals↗
PubMed1983

Biochemical, functional and behavioral evaluation of a series of novel antipsychotic-like agents.

Two ethyl phenylpiperazine substituted isochromans and a related benzoxepine were discovered to have antipsychotic-like properties in animal screening models. Further evaluation of these compounds disclosed that, like neuroleptics, they blocked dopamine-stimulated adenylate cyclase, displaced 3H-spiperone in vitro, altered dopamine synthesis, and decreased conditioned avoidance and intracranial self-stimulation behavior. In contrast to classical neuroleptics but like clozapine, these compounds did not block apomorphine or amphetamine-induced chewing stereotypy in rats, raise serum prolactin concentrations, or increase 3H-spiperone binding after chronic dosing. However, unlike clozapine, the compounds of this series did not displace 3H-spiperone in either of two in vivo paradigms nor did they alter striatal acetylcholine concentrations. Taken together these data suggest that these isochroman and benzoxepine analogs would most probably not cause neuroleptic extrapyramidal side effects or prolactin elevations clinically. However, due to their atypical nature, their antipsychotic potential can only be assessed with certainty by careful clinical studies.

Adenylyl Cyclase Inhibitors↗
PubMed1983

Discriminative stimulus properties of nalorphine in the rhesus monkeys.

The discriminative stimulus properties of nalorphine were studied in rhesus monkeys trained to discriminate i.m. injections of nalorphine (1 mg/kg) from saline. During training, a two-lever paradigm was employed where a single, 3-min extinction schedule was followed by fixed-ratio-20 schedules of food presentation. During the fixed-rate schedules, responses on one of the two levers produced food when nalorphine had been administered and responses on the other lever produced food when saline had been administered. During stimulus generalization tests, responses on either lever produced food under the fixed-ratio schedule. The discriminative stimulus effects of nalorphine were antagonized by naloxone which, by itself, did not generalize to nalorphine. The kappa opiate agonists, ethylketocyclazocine, U-50,488, bremazocine, tifluadom, as well as two mixed kappa-sigma agonists, dl-cyclazocine and dl-N-allylnormetazocine (SKF-10047), generalized to nalorphine with the following potency ranking order: bremazocine greater than ethylketocyclazocine greater than tifluadom greater than cyclazocine greater than U-50,488 greater than N-allylnormetazocine greater than nalorphine. The levo-isomers of cyclazocine, N-allylnormetazocine or U-50,488 generalized to nalorphine whereas the dextroisomers did not. Generalization to nalorphine did not occur with the mu opiate agonists, morphine, methadone and meperidine, or the nonopiate compounds, phencyclidine, ketamine and chlorpromazine. The results suggest that a kappa opiate receptor mechanism mediates the discriminative effects of nalorphine in the rhesus monkey, which may also be involved with the naloxone-sensitive, sedative and dysphoric effects of nalorphine in humans.

Animals↗
PubMed1983

Disruption of brightness discrimination in a shock avoidance task by phencyclidine and its antagonism in rats.

Rats were trained to make a simultaneous brightness discrimination in order to avoid or escape foot shocks in an automated Y-maze. Brightness discrimination was completely disrupted by phencyclidine (PCP, 3 mg/kg), ketamine (30 mg/kg) and dexoxadrol (10 mg/kg). At these doses, there was increased locomotor activity between trials. The number of movement attempts to avoid shock during a trial were either unchanged or reduced. Several drugs with various clinical applications (chlorpromazine, haloperidol, diazepam, pentobarbital, d-amphetamine, propranolol, clonidine and prazosin) did not impair brightness discrimination in behavioral stimulant or depressant doses. The levoisomer of dexoxadrol, levoxadrol, was also inactive. Daily administration of PCP for 5 consecutive days produced progressive increases in locomotor stimulation with no tolerance to effects on brightness disruption. The disruption of brightness discrimination by PCP was not reversed by chlorpromazine, haloperidol, diazepam, propranolol or apomorphine at doses which reduced the locomotor stimulation by PCP. Both locomotor stimulation and discrimination disruption were blocked by prazosin and clonidine. A central adrenergic mechanism is implicated for some behavioral effects of PCP.

Anesthetics, Dissociative↗
PubMed1977

Behavior maintained under second-order schedules of intravenous morphine injection in squirrel and rhesus monkeys.

Under second-order schedules of morphine injection, high rates of responding by squirrel and rhesus monkeys were maintained when morphine was injected intravenously only at the end of each session. Every 30th key-pressing response during a 60-min interval produced a 2-s light; the first 30-response component completed after 60 min produced both the light and intravenous injection of morphine. A mean rate of approximately one response per second was maintained by doses of morphine ranging from 0.75-1.5 mg/kg. A pause in responding after each light presentation was followed by rapid responding until the light was produced again; pauses became shorter as the 60-min interval progressed. When brief light presentations were omitted, but morphine was still injected, response rates decreased and patterns of responding were altered. When saline injections were substituted for morphine injections, but the brief light was still presented, responding decreased markedly within three to five sessions and patterns of responding were altered.

Animals↗