ArticleBritish journal of pharmacology2007
F15063, a compound with D2/D3 antagonist, 5-HT 1A agonist and D4 partial agonist properties. II. Activity in models of positive symptoms of schizophrenia.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
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- Evaluation of SYA16263 as a new potential antipsychotic agent without catalepsy.Pharmacology, biochemistry, and behavior · 2019Article
- Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands.Bioorganic & medicinal chemistry · 2016Article
- Further evaluation of the tropane analogs of haloperidol.Bioorganic & medicinal chemistry letters · 2014Article
- Evaluation of the potential of antipsychotic agents to induce catalepsy in rats: assessment of a new, commercially available, semi-automated instrument.Pharmacology, biochemistry, and behavior · 2014Article
- Exploring the role of 5-HT1A receptors in the regulation of prepulse inhibition in mice: implications for cross-species comparisons.ACS chemical neuroscience · 2013Article
- Serotonin-glutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins.Psychopharmacology · 2013Review
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- Evaluation of the behavioral and pharmacokinetic profile of SYA013, a homopiperazine analog of haloperidol in rats.Pharmacology, biochemistry, and behavior · 2012Article
- Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties.Psychopharmacology · 2011Review
- Cross-species assessments of motor and exploratory behavior related to bipolar disorder.Neuroscience and biobehavioral reviews · 2010Review
- The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice.Behavioural pharmacology · 2010Article
- Realistic expectations of prepulse inhibition in translational models for schizophrenia research.Psychopharmacology · 2008Review
- Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties.Naunyn-Schmiedeberg's archives of pharmacology · 2007Article
- F15063, a potential antipsychotic with dopamine D(2)/D(3) antagonist, 5-HT(1A) agonist and D(4) partial agonist properties: (IV) duration of brain D2-like receptor occupancy and antipsychotic-like activity versus plasma concentration in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2007Article
- F15063, a compound with D2/D3 antagonist, 5-HT 1A agonist and D4 partial agonist properties. III. Activity in models of cognition and negative symptoms.British journal of pharmacology · 2007Article
- F15063, a potential antipsychotic with D2/D3 antagonist, 5-HT 1A agonist and D4 partial agonist properties. I. In vitro receptor affinity and efficacy profile.British journal of pharmacology · 2007Article
- Optimisation of anti-psychotic therapeutics: a balancing act?British journal of pharmacology · 2007Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeF15063 is a high affinity D(2)/D(3) antagonist, D(4) partial agonist, and high efficacy 5-HT(1A) agonist, with little affinity (40-fold lower than for D(2) receptors) at other central targets. Here, the profile of F15063 was evaluated in models of positive symptoms of schizophrenia and motor side-effects. EXPERIMENTAL APPROACH: Rodent behavioural tests were based on reversal of hyperactivity induced by psychostimulants and on measures of induction of catalepsy and 'serotonin syndrome'. KEY
resultsF15063 potently (ED(50)s: 0.23 to 1.10 mg kg(-1) i.p.) reversed methylphenidate-induced stereotyped behaviors, blocked d-amphetamine and ketamine hyperlocomotion, attenuated apomorphine-induced prepulse inhibition (PPI) deficits, and was active in the conditioned avoidance test. In mice, it reversed apomorphine-induced climbing (ED(50)=0.30 mg kg(-1) i.p.). F15063, owing to its 5-HT(1A) agonism, did not produce (ED(50)>40 mg kg(-1) i.p.) catalepsy in rats and mice, a behavior predictive of occurrence of extra-pyramidal syndrome (EPS) in man. This absence of cataleptogenic activity was maintained upon sub-chronic treatment of rats for 5 days at 40 mg kg(-1) p.o. Furthermore, F15063 did not induce the 'serotonin syndrome' in rats (flat body posture and forepaw treading: ED(50) >32 mg kg(-1) i.p.). CONCLUSIONS AND IMPLICATIONS: F15063 conformed to the profile of an atypical antipsychotic, with potent actions in models of hyperdopaminergic activity but without inducing catalepsy. These data suggest that F15063 may display potent antipsychotic actions with low EPS liability. This profile is complemented by a favourable profile in rodent models of negative symptoms and cognitive deficits of schizophrenia (companion paper).
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