The effect of olanzapine on cognition and psychomotor function in healthy elderly volunteers

Taylor, Nicholas F.; Beuzen, J.N.; Wesnes, K. A.; Wood, A. J.

doi:10.1016/0920-9964(96)85439-9

Cited by 9 publications

(2 citation statements)

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“…Olanzapine also antagonized apomorphine-induced climbing behavior, 5-hydroxytryptophan (5-HTP)-induced head twitches and oxotremorine-induced tremor in mice (Moore et al 1992), indicative of antagonism of DA, 5HT 2 and muscarinic receptors, respectively. In vivo neurochemical and pharmacological studies further demonstrated that olanzapine potently blocked DA D 2 and 5HT 2A receptors and to a lesser extent 1 -adrenergic and muscarinic receptors (Moore et al 1992;Bymaster et al 1996b), consistent with its favorable clinical profile of low incidence of anticholinergic effects such as dry mouth, constipation (Beasley et al 1996a,b) and cognitive impairment (Taylor et al 1996).…”

Section: Introductionmentioning

confidence: 90%

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D 1 , D 2 , D 3 , 5HT 2A and muscarinic receptors

1999

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The atypical antipsychotic olanzapine was compared to other atypical as well as typical antipsychotic agents for in vivo occupancy of D1, D2, D3, 5HT2, and muscarinic receptors in rat brain. Blockade of D2 receptors was determined by measuring the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). To assess the interaction with phosphoinositide (PI)-coupled 5HT2A and muscarinic receptors in vivo, we used a novel radiometric technique to measure in vivo PI hydrolysis. The antagonism of olanzapine and other antipsychotic agents on 5HT2A and muscarinic receptors was determined by in vivo blockade of PI hydrolysis, stimulated by the 5HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) or the muscarinic agonist pilocarpine. Olanzapine inhibited 5HT2, D2, and D3 in vivo binding with high potency (ID50=0.15, 0.6 and 1.2 mg/kg, IP, respectively), while inhibiting D1 and muscarinic in vivo binding with much less potency (ID50 > 10 mg/kg, IP). The binding of olanzapine to D2 receptors in neostriatum was well correlated with the increase of DOPAC (ED200 = 0.8 mg/kg, IP) in vivo, indicating dopamine D2 antagonism. In vivo PI hydrolysis was increased by DOI in frontal cortex and by pilocarpine in hippocampus up to 2- and 7-fold above the basal level, respectively. The agonist-induced increases in PI hydrolysis were fully blocked by the 5HT2A antagonist MDL100907 and the muscarinic antagonist scopolamine, indicating the mediation by 5HT2A receptors in frontal cortex and PI-coupled muscarinic receptors (ml, m3, and m5) in hippocampus, respectively. Olanzapine was about 8-fold more potent in vivo in blocking DOI-induced stimulation of PI hydrolysis (ID50 = 0.1 mg/kg, IP) than pilocarpine-induced stimulation of PI hydrolysis (ID50 = 0.8 mg/kg, IP). In conclusion, olanzapine is more potent in blocking the 5HT2A receptor than D1, D2, D3 and muscarinic receptors in vivo, consistent with its favorable clinical profiles. In addition, the novel in vivo PI hydrolysis assay proved to be a useful and reliable in vivo method to assess the functional efficacy of compounds that interact with the 5HT2 and muscarinic receptors.

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Section: Introductionmentioning

confidence: 90%

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D 1 , D 2 , D 3 , 5HT 2A and muscarinic receptors

1999

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“…Patients treated with olanzapine have a significantly lower risk of developing tardive dyskinesia than patients treated with haloperidol . Olanzapine has also been associated with a low incidence of cognitive impairment in healthy, elderly subjects (Taylor et al 1996).…”

Section: Introductionmentioning

confidence: 99%

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

Porter¹,

McCallum²,

Varvel³

et al. 2000

Psychopharmacology

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In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine's discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.

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Olanzapine for schizophrenia

Duggan¹,

Fenton²,

Dardennes³

et al. 2000

Cochrane Database of Systematic Reviews

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The effect of olanzapine on cognition and psychomotor function in healthy elderly volunteers

Cited by 9 publications

References 0 publications

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D 1 , D 2 , D 3 , 5HT 2A and muscarinic receptors

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D 1 , D 2 , D 3 , 5HT 2A and muscarinic receptors

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

Olanzapine for schizophrenia

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