The highly selective 5‐hydroxytryptamine (5‐HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test

  title={The highly selective 5‐hydroxytryptamine (5‐HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test},
  author={Jignesh G Patel and Gerd D. Bartoszyk and E Edwards and Charles R. Ashby},
We examined the effect of the highly selective 5‐hydroxytryptamine (5‐HT)2A receptor antagonist 7‐{4‐[2‐(4‐fluoro‐phenyl)‐ethyl]‐piperazine‐1‐carbonyl}‐1H‐indole‐3‐carbonitrile HCl (EMD 281014) in congenital learned helpless male rats in the forced swim test. The administration of EMD‐281014 (0.3–30 mg/kg i.p.) to congenital learned helpless rats dose‐dependently and significantly (at 10 and 30 mg/kg) decreased immobility and increased swimming compared to vehicle‐treated animals. Thus, EMD… 
A novel 5-HT2A receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: Approaching early-onset antidepressants
This investigation revealed that 5-HT(2A) receptor antagonism is the principal mechanism behind the antidepressant-like effects of BIP-1, and propound the combination of 4-benzo-3-yl piperazin-1-yl and methyl)-6-chloroindolin-2-one as a likely strategy to achieve an early-onset of antidepressant action.
Selective serotonin 5-HT2A receptor antagonist EMD 281014 improves delayed matching performance in young and aged rhesus monkeys
These experiments, conducted in a non-human primate model, suggest that selective 5HT2A antagonists such as EMD 281014 could offer therapeutic benefit to younger and older psychiatric patients by improving working memory function.
5-HT2A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system
The blockade of the 5-HT2AR may strengthen the antidepressant-like effect of escitalopram by facilitating the enhancement of the brain NE transmission and provide support for the use of atypical antipsychotics with SSRIs as a relevant antidepressant augmentation strategy.
Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal
5- HT(2A) receptor antagonist and 5-HT(2C) receptor agonists exhibited effects similar to antidepressant drugs and abolished the depression-like effects in nicotine-withdrawn rats, and should be considered as adjuncts to smoking cessation therapy, to ameliorate abstinence-induced depressive symptoms.
Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.
The present data suggest S-MEPH may be a possible structural and pharmacological template to develop maintenance therapy for acute anxiety and depression during early withdrawal from psychostimulant abuse.
Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test
A physiological model of performance in the rat FST has been proposed involving the regulation of 5-HT transmission by corticotropin releasing factor (CRF), which is based on extensive evaluation of agonists and antagonists of individual 5- HT receptor subtypes.
Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain‐derived neurotrophic factor, β‐catenin and antidepressant‐like effects
The involvement of neuroplasticity pathways and/or the 5‐hydroxytryptaminergic system in the antidepressant‐like effect of this combined treatment, given subchronically is studied.
5-HT 2 ligands in the treatment of anxiety and depression
Introduction: One third of depressed patients do not respond adequately to conventional antidepressants including the selective serotonin reuptake inhibitors (SSRIs). Therefore, multi-target drugs or
Antidepressant Effect of Cnestis ferruginea Vahl ex DC (Connaraceae): Involvement of Cholinergic, Monoaminergic and L-arginine-nitric Oxide Pathways.
C. ferruginea exerts its antidepressant-like action through interaction with α-adrenoceptor, dopamine D2,5-HT2B, 5-HT6 and muscarinic cholinergi1c receptors as well as L-arginine-nitric oxide systems and could be used as adjuvant with conventional antidepressants in the treatment of major depressive disorder.
5-HT2 ligands in the treatment of anxiety and depression
This review synthesizes the current literature about the behavioral, electrophysiological and neurochemical effects of 5-HT2 receptors ligands on the monoaminergic systems but also on adult hippocampal neurogenesis to shed some light on the preclinical evidence supporting the use of 5 -HT2A and/or 5- HT2C receptor antagonists such as antipsychotics, as potential effective adjuncts in SSRIs-resistant depression.


In vitro autoradiography of serotonin 5‐HT2A/2C receptor‐activated G protein: Guanosine‐5′‐(γ‐[35S]thio)triphosphate binding in rat brain
Autoradiography revealed a similar localization of DOI‐ and 5‐HT‐stimulated binding of [35S]GTPγS in distinct areas of prefrontal and parietal cortex, consistent with previously reported 5‐ HT2A receptor distribution.
EMD 281014, a new selective serotonin 5-HT2A receptor antagonist.
The 5-HT2A receptor ligand 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) selectively binds to human (h) and rat 5- HT2A receptors, demonstrating unique selectivity and efficacy.
Antisense inhibition of 5-hydroxytryptamine2a receptor induces an antidepressant-like effect in mice.
It is reported that down-regulation of the 5-HT2A receptor by intracerebroventricular injection of antisense oligonucleotides resulted in an antidepressant-like effect in mice and suggested that receptor down- regulation may be an essential part of the antidepressant drug action.
Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants
This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST), and showed that SSRIs are not false negatives in the FST.
Modulation of learned helplessness by 5-hydroxytryptamine2A receptor antisense oligodeoxynucleotides
The view that central 5HT, mediated by the 5HT2A receptor, participates in regulating behaviors that are affected by inescapable stress, and that the induction of behavioral depression may be specifically regulated via serotonergic pathways that terminate in this hippocampal subfield is supported.
Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims.
The hypothesis that suicide completed by violent methods is associated with reduced presynaptic serotonergic activity that has generated compensatory upregulation of the postsynaptic serotonin2 receptor sites is supported and antidepressant pharmacotherapies specifically downregulate cortical beta-adrenergic and/or serotonin2 receptors in depressed subjects are investigated.
Behavioural despair in rats: a new model sensitive to antidepressant treatments.
Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
Imaging of the serotonergic system: interactions of neuroanatomical and functional abnormalities of depression
Analysis of the 5-HT2 receptor using positron emission tomography has suggested that this receptor may not be altered significantly in the depressed brain but may increase in response to antidepressant treatment, supported by studies in secondary "poststroke" depression that have shown that elevations in 5- HT2 receptor density correlated with the alleviation of symptoms of depressed mood.
Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims.
It is concluded that suicide is associated with a localized increase in 5-HT2 binding sites, which is linked to a deficiency in serotonin neurotransmission.