Seroquel: behavioral effects in conventional and novel tests for atypical antipsychotic drug

Migler, Bernard; Warawa, E. J.; Malick, Jeffrey B.

doi:10.1007/bf02244925

Cited by 97 publications

(59 citation statements)

References 13 publications

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“…The results with amperozide are in agreement with other literature data as well (Gustafsson and Christensson 1990b;Kimura et al 1993). Surprisingly, quetiapine has also a profile simi- Figure 1 and Migler et al 1993). The marginal selectivity (hypermotility versus stereotypy) of risperidone and olanzapine is most likely caused by their more predominating DA antagonism compared with clozapine and sertindole (Figure 1).…”

supporting

confidence: 39%

“…In a more recent summary article from the same group, a complete series of novel APDs was investigated, but only qualitative results were shown, precluding any critical evaluation (Goldstein 1995). Quetiapine has also been administered weekly to drug-naive monkeys and induced negligible dystonia compared with that seen in a haloperidol-treated group (Migler et al 1993).The mechanism underlying the differences in dystonia-inducing potencies between novel APDs is not known, but it appears that all APDs with potent DA 0 2 antagonistic actions induce dystonia. Dystonias are effectively reversed by additional treatment with a muscarinic antagonist, which is used as an antidote in the experiments if unacceptable dystonias develop.…”

mentioning

confidence: 41%

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Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

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The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal modelsDuring the last decade there has been a dramatic increase in the efforts to develop novel antipsychotic drugs (APDs) with improved clinical efficacy and fewer or no extrapyramidal side effects (EPS) than the classical APDs such as haloperidol and fluphenazine. These efforts were undoubtedly inspired by the previous development of clozapine, which fulfilled these criteria to a large extent, although having other troublesome side From the Pharmacological Research, H. Lundbeck A/S, Ohiliavej 9, DK-2500, Copenhagen-Valby, Denmark.Address correspondence to: J0rn Arnt, Pharmacological Research, H. Lundbeck A/5, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark.Received January 6, 1997; revised June 26, 1997; accepted July 7, 1997. effects (Baldessarini and Frankenburg 1991; Coward 1992;Wagstaff and Bryson 1995;Buchanan 1995; Ashby and Wang 1996).The novel APDs were assigned the popular term "atypical antipsychotic" drugs to differentiate them from the classic or "typical" APDs or neuroleptics. The most widely accepted definition of a neuroleptic is a compound that has antipsychotic activity and induces EPS with high frequency. The definition of "a typicality" was equivocal, however, because the term was often used for drugs before any clinical results were available. For example, the term was applied to a compound that induced little or no catalepsy in rats, and that was effective in another model believed to reflect antipsychotic activity, e.g., inhibition of O-amphetamine (AMPH)-induced hypermotility. A more precise definition is to base it solely on clinical evidence as a wide differentiation between the dosages used to control psychosis and those inducing EPS-or on other aspects of clinical superior-0893-133X/98/$19.00 PI! 50893-133X(97)00112-7 64 J. Arnt and T. Skarsfeldt ity over classic APDs, e.g., efficacy on negative symptoms of schizophrenia or in drug-resistant patients (for recent review, see Kinan and Lieberman 1996). However, because these very different characteristics are difficult to incorporate in a common definition, we suggest that the terminology "atypical" is best avoided. Indeed, as will be discussed, novel APDs show many individual differences.The suggested alternative terminology "novel APO" is also not precise, but it can be defined as a compound that has been shown to inhibit positive symptoms of schizophrenia and has either been recently launched or is in phase II/III clinical development. Their specific profiles can be described more precisely, e.g., EPS-free APO, etc. It is not anticipated that novel APDs will be marketed in the future, unless hav...

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supporting

confidence: 39%

mentioning

confidence: 41%

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

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“…The next day, inhibition of apomorphine-induced eye blinking was measured after Brexpiprazole, A Novel Serotonin-Dopamine Activity Modulator pretreatment with brexpiprazole. The measurements were conducted according to the literature (Migler et al, 1993;Kleven and Koek, 1996).…”

Section: Apomorphine-induced Eye Blinking In Monkeysmentioning

confidence: 43%

Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

Maeda¹,

Lerdrup²,

Sugino³

et al. 2014

J Pharmacol Exp Ther

108

116

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Brexpiprazole piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator with partial agonist activity at serotonin 1A (5-HT 1A ) and D 2/3 receptors, combined with potent antagonist effects on 5-HT 2A , a 1B -, and a 2C -adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response (ED 50 = 6.0 mg/kg), apomorphine-or D-amphetamine-induced hyperactivity (ED 50 = 2.3 and 0.90, respectively), and apomorphine-induced stereotypy (ED 50 = 2.9) in rats at clinically relevant D 2 receptor occupancies. Brexpiprazole also potently inhibited apomorphine-induced eye blinking in monkeys. The results suggest that brexpiprazole has antipsychotic potential. Brexpiprazole induced catalepsy (ED 50 = 20) well above clinically relevant D 2 receptor occupancies, suggesting a low risk for extrapyramidal side effects. Subchronic treatment with phencyclidine (PCP) induced cognitive impairment in both novel object recognition (NOR) and attentional set-shifting (ID-ED) tests in rats. Brexpiprazole reversed the PCP-induced cognitive impairment in the NOR test at 1.0 and 3.0 mg/kg, and in the ID-ED test at 1.0 mg/kg. However, aripiprazole (10 mg/kg) was ineffective in both tests, despite achieving relevant D 2 occupancies. In the NOR test,

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“…Using methods previously standardized (Wadenberg et al 2000), the present study investigated the relationship between DA D 2 receptor occupancy and catalepsy in rats for one typical, haloperidol (Janssen 1967), and three atypical, risperidone (Janssen et al 1988), olanzapine (Moore et al 1992), and quetiapine (Migler et al 1993), antipsychotic compounds. In addition, dose response curves for haloperidol, risperidone, olanzapine, and quetiapine were also established in the conditioned avoidance response test for antipsychotic activity and related to D 2 occupancies.…”

mentioning

confidence: 46%

Dopamine D2 Receptor Occupancy Is a Common Mechanism Underlying Animal Models of Antipsychotics and Their Clinical Effects

Wadenberg

Soliman

VanderSpek

et al. 2001

Neuropsychopharmacology

223

167

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Conditioned avoidance response (CAR) behavior and catalepsy (CAT) are the standard preclinical tests used to predict antipsychotic activity and motor side-effect liability, respectively. Recent data in patients showUsing this technique, Farde et al. (1992) suggested that both antipsychotic response and extrapyramidal side effects (EPS) may be related to D 2 receptor occupancyalbeit with different thresholds. With typical antipsychotics, a D 2 receptor occupancy in the range of 70% was associated with clinical response while EPS emerged at a D 2 receptor occupancy Ͼ 80% (Farde et al. 1992;Nordstrom et al. 1993). This relationship has been confirmed by subsequent clinical studies. In a double-blind PET study with haloperidol, Kapur et al. found that clinical response was manifest at 65-70% D 2 receptor occupancy, but only patients with a D 2 receptor occupancy Ͼ 78% showed signs of EPS (Kapur et al. 2000a).Newly synthesized potentially antipsychotic drugs are tested in the catalepsy (CAT) test (for EPS liability) and the conditioned avoidance response (CAR) test (for

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Seroquel: behavioral effects in conventional and novel tests for atypical antipsychotic drug

Cited by 97 publications

References 13 publications

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

Dopamine D2 Receptor Occupancy Is a Common Mechanism Underlying Animal Models of Antipsychotics and Their Clinical Effects

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