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N C Tye

Publications and source records attributed to N C Tye.

11 recordsLinked to original sources
PubMed1996

Radioreceptor binding profile of the atypical antipsychotic olanzapine.

The affinities of olanzapine, clozapine, haloperidol, and four potential antipsychotics were compared on binding to the neuronal receptors of a number of neurotransmitters. In both rat tissues and cell lines transfected with human receptors olanzapine had high affinity for dopamine D1, D2, D4, serotonin (5HT)2A, 5HT2C, 5HT3, alpha 1-adrenergic, histamine H1, and five muscarinic receptor subtypes. Olanzapine had lower affinity for alpha 2-adrenergic receptors and relatively low affinity for 5HT1 subtypes, GABAA, beta-adrenergic receptors, and benzodiazepine binding sites. The receptor binding affinities for olanzapine was quite similar in tissues from rat and human brain. The binding profile of olanzapine was comparable to the atypical antipsychotic clozapine, while the binding profiles for haloperidol, resperidone, remoxipride, Org 5222, and seroquel were substantially different from that of clozapine. The receptor binding profile of olanzapine is consistent with the antidopaminergic, antiserotonergic, and antimuscarinic activity observed in animal models and predicts atypical antipsychotic activity in man.

Animals↗
PubMed1992

The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent.

Olanzapine (LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel "atypical" antipsychotic agent with 5-hydroxytryptamine2.dopamine D1/D2 antagonist activity and anticholinergic properties. In behavioral studies, olanzapine (1.25-10 mg/kg, p.o.) antagonizes apomorphine-induced climbing behavior in mice, demonstrating that the compound possesses D1/D2 antagonist activity in vivo. Olanzapine (0.3-20 mg/kg, p.o.) antagonizes 5-hydroxytryptophan-induced head twitches in mice at doses much lower than those required to block the climbing response, confirming that in vivo, the compound is a more potent 5-hydroxytryptamine2 antagonist than dopamine antagonist. Olanzapine (2.5-10 mg/kg, p.o.) also antagonized oxotremorine-induced tremor in mice. In a conditioned avoidance paradigm in rats, olanzapine inhibits the avoidance response with an ED50 of 4.7 mg/kg p.o; however, unlike other antipsychotic agents, catalepsy is only observed at much higher doses (ED50 39.4 mg/kg, p.o.). These data would suggest that the compound will be less likely to produce undesirable extrapyramidal symptoms. Unlike "typical" antipsychotics, olanzapine (1.25-5 mg/kg p.o.) increases responding during the conflict component of a modified Geller Seifter test, demonstrating that the compound may also possess anxiolytic activity. In another series of experiments, olanzapine (1.25 mg/kg, i.p.) produced clozapine-appropriate responding in a drug discrimination model in which animals had been trained to discriminate clozapine (5 mg/kg, i.p.) from vehicle. On the basis of these results, it would therefore be predicted that olanzapine will have an atypical profile and will be less likely to induce undesirable extrapyramidal symptoms than currently available drugs.

Animals↗
PubMed1979

Differential enhancement of locomotor activity by dopamine agonists following chronic neuroleptic treatment: an animal model of tardive dyskinesia.

Animals were administered clozapine or haloperidol for 22 days. Following treatment they were challenged with an apomorphine ester or lergotrile. Only haloperidol-treated animals exhibited significantly enhanced responses to apomorphine ester whereas administration of lergotrile potentiated locomotor activity in both treated groups. The results suggest that the use of different dopaminergic agonists may help to dissociate receptor supersensitivity arising from the antipsychotic actions of neuroleptics from that leading to the development of undesirable side effects.

Animals↗
PubMed1977

Two dopamine receptors: supportive evidence with the rat rotational model.

Di-isobutyryl apomorphine (5 mg/kg i.p.) and lergotrile (5 mg/kg i.p.) produce long lasting turning behaviour in rats with 6-hydroxydopamine lesions at the level of the substantia nigra. Haloperidol (1.5 and 3.0 mg/kg p.o.) blocks the rotational behaviour due to the apomorphine ester but has no effect on lergotrile turning. Clozapine (10 and 20 mg/kg p.o.) blocks the lergotrile turning but stimulates the rotational behaviour produced by the apomorphine ester. The results support the concept of two anatomically separate dopamine receptors and their relevance to the study of antipsychotic activity is discussed.

Animals↗
PubMed1977

Benzodiazepines and discrimination behaviour: dissociation of response and sensory factors.

Ten London pigeons were trained on a schedule which allowed concurrent measurement of motor and exteroceptive sensory changes. The task involved a conditional colour discrimination contingent upon the completion of a fixed interval schedule of responding. As a preliminary pharmacological study the effects of the benzodiazepines, chlordiazepoxide and flurazepam were investigated. Both drugs enhanced perseverative responding (after completion of the FI), and to a variable degree responding during the FI, although there was no evidence for an increase in responding during the inter-trial-intervals. On the other hand, no marked changes in discrimination performance were observed. It is concluded that the most significant effects of these benzodiazepines are on motor mechanisms.

Animals↗
PubMed1975

Chlordiazepoxide and isolation induced timidity in rats.

The effects of chlordiazepoxide (CDP) on emergence behavior was examined in socially reared and isolation reared rats. It was found that low doses of CDP decreased the emergence times of isolated animals but had little effect on the emergence of social animals. At higher doses the drug retarded emergence in all groups but there were no differential effects. The results do not support claims that rearing conditions influence the susceptability of rats to CNS depressants, rather they suggest that particular levels of CDP selectively influence "emotional" behavior.

Animals↗
PubMedDate not supplied

Chlordiazepoxide and preference for free food in rats.

Rats continued to lever press for food when a bowl of free food was placed in the experimental chamber. Chlordiazepoxide increased the amount of free food consumed, and tended to reduce the amount of lever pressing. It is argued that the drug decreased container neophobia in the animals, rather than acting like an increase in food deprivation.

Animals↗