Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia

Barnes, Thomas R. E.; McPhillips, Mike A.

doi:10.1097/00004850-199803003-00009

Cited by 71 publications

(45 citation statements)

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“…EPS continues to be a clinically important problem in the treatment of schizophrenia and is an important cause of reduced patient compliance with therapy (Barnes and McPhillips, 1998). In the present study, lurasidone did not induce EPS in various animal behavioral tests at doses up to 1000 mg/kg.…”

Section: Discussioncontrasting

confidence: 39%

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity

Ishibashi¹,

Horisawa²,

Tokuda³

et al. 2010

J Pharmacol Exp Ther

384

304

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Lurasidone [(3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; SM-13496] is an azapirone derivative and a novel antipsychotic candidate. The objective of the current studies was to investigate the in vitro and in vivo pharmacological properties of lurasidone. Receptor binding affinities of lurasidone and several antipsychotic drugs were tested under comparable assay conditions using cloned human receptors or membrane fractions prepared from animal tissue. Lurasidone was found to have potent binding affinity for dopamine D 2 , 5-hydroxytryptamine 2A (5-HT 2A ), 5-HT 7 , 5-HT 1A , and noradrenaline ␣ 2C receptors. Affinity for noradrenaline ␣ 1 , ␣ 2A , and 5-HT 2C receptors was weak, whereas affinity for histamine H 1 and muscarinic acetylcholine receptors was negligible. In vitro functional assays demonstrated that lurasidone acts as an antagonist at D 2 and 5-HT 7 receptors and as a partial agonist at the 5-HT 1A receptor subtype. Lurasidone showed potent effects predictive of antipsychotic activity, such as inhibition of methamphetamine-induced hyperactivity and apomorphine-induced stereotyped behavior in rats, similar to other antipsychotics. Furthermore, lurasidone had only weak extrapyramidal effects in rodent models. In animal models of anxiety disorders and depression, treatment with lurasidone was associated with significant improvement. Lurasidone showed a preferential effect on the frontal cortex (versus striatum) in increasing dopamine turnover. Anti-␣ 1 -noradrenergic, anticholinergic, and central nervous system (CNS) depressant actions of lurasidone were also very weak. These results demonstrate that lurasidone possesses antipsychotic activity and antidepressant-or anxiolytic-like effects with potentially reduced liability for extrapyramidal and CNS depressant side effects.

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Section: Discussioncontrasting

confidence: 39%

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity

Ishibashi¹,

Horisawa²,

Tokuda³

et al. 2010

J Pharmacol Exp Ther

384

304

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“…21 Does switching from typical to atypical DRBAs reduce TDS symptoms? Atypical antipsychotics are believed to have a lower propensity to cause TDS than typical DRBAs, [22][23][24][25] suggesting that changing from typical to atypical DRBAs might reduce TDS symptoms. Current evidence is limited to Class IV studies [26][27][28][29][30] with conflicting results.…”

mentioning

confidence: 99%

Evidence-based guideline: Treatment of tardive syndromes

et al. 2013

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Objective: To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy?Methods: PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched . Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Results and recommendations:Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B 6 , selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, a-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U). Tardive syndromes (TDS) are disorders that fulfill the following criteria: history of at least 3 months' total cumulative neuroleptic exposure during which the exposure can be continuous or discontinuous, presence of at least "moderate" abnormal involuntary movements in one or more body areas or at least "mild" movements in 2 or more body areas, and absence of other conditions that might produce abnormal involuntary movements.1 Various involuntary movements, including lingual-facial-buccal movements, are recognized as tardive dyskinesia (TDD) symptoms. TDS includes not only lingual-facial-buccal dyskinesia but also the variant forms, collectively termed tardive syndromes. [2][3][4][5][6][7][8] In this guideline, tardive dyskinesia encompasses all forms of persistent dyskinesia caused by dopamine receptor blocking agents (DRBAs).TDS prevalence is estimated to be 30% in outpatients with schizophrenia treated with neuroleptics.9-11 TDS †Deceased.

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“…Catalepsy is associated with high dopamine D2 receptor occupancy (Crocker and Hemsley, 2001) and is predictive of extrapyramidal side effects observed in humans (Kurz et al, 1995). One of the hallmarks of atypical antipsychotics is the reduced liability for extrapyramidal side effects (Barnes and McPhillips, 1998;Kurz et al, 1995;Worrel et al, 2000). This is modeled in rodents by the lack of ability to produce catalepsy (Hoffman and Donovan, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Extrapy- jpet.aspetjournals.org ramidal side effects cause subjective discomfort and distress and likely contribute to poor compliance with prescribed medication regimens (Barnes and McPhillips, 1998). The reduced liability of such side effects along with equal or greater efficacy for the treatment of psychotic symptoms have lead to the success of atypical antipsychotic treatment.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of AC-90179 [2-(4-Methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide Hydrochloride]: A Selective Serotonin 2A Receptor Inverse Agonist

Vanover¹,

Harvey²,

Son³

et al. 2004

J Pharmacol Exp Ther

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The primary purpose of the present series of experiments was to characterize the in vitro and in vivo pharmacology profile of 2-(4-methoxy-phenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide hydrochloride (AC-90179), a selective serotonin (5-HT 2A ) receptor inverse agonist, in comparison with the antipsychotics haloperidol and clozapine. The secondary purpose was to characterize the pharmacokinetic profile of AC-90179. Like all atypical antipsychotics, AC-90179 shows high potency as an inverse agonist and competitive antagonist at 5HT 2A receptors. In addition, AC-90179 exhibits antagonism at 5HT 2C receptors. In contrast, AC-90179 does not have significant potency for D 2 and H 1 receptors that have been implicated in the dose-limiting side effects of other antipsychotic drugs. The ability of AC-90179 to block 5-HT 2A receptor signaling in vivo was demonstrated by its blockade of the rate-decreasing effects of the 5-HT 2A agonist, (Ϯ)-2,5-dimethoxy-4-iodoamphetamine hydrochloride, under a fixed ratio schedule of reinforcement. Similar to clozapine and haloperidol, AC-90179 attenuated phencyclidineinduced hyperactivity. Although haloperidol impaired acquisition of a simple autoshaped response and induced cataleptic-like effects at behaviorally efficacious doses, AC-90179 and clozapine did not. Furthermore, unlike haloperidol and clozapine, AC-90179 did not decrease spontaneous locomotor behavior at efficacious doses. Limited oral bioavailability of AC-90179 likely reflects rapid metabolism rather than poor absorption. Taken together, a compound with a similar pharmacological profile as AC-90179 and with increased oral bioavailability may have potential for the treatment of psychosis.

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Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia

Cited by 71 publications

References 0 publications

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity

Evidence-based guideline: Treatment of tardive syndromes

Pharmacological Characterization of AC-90179 [2-(4-Methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide Hydrochloride]: A Selective Serotonin 2A Receptor Inverse Agonist

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Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia

Cited by 71 publications

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Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT7) and 5-HT1A Receptor Activity

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT7) and 5-HT1A Receptor Activity

Evidence-based guideline: Treatment of tardive syndromes

Pharmacological Characterization of AC-90179 [2-(4-Methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide Hydrochloride]: A Selective Serotonin 2A Receptor Inverse Agonist

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Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity

Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT₇) and 5-HT_1A Receptor Activity