Disease relevance of nemonapride

• A potent and selective D-2 antagonist, YM-09151 (YM-09151-2) at a dose of 1.2 mg/kg, SC and a selective D-1 antagonist, SCH 23390 at 1.0 mg/kg, SC induced catalepsy in rats [1].
• Effective doses of terguride had no systematic effect on motor activity or muscle rigidity, whereas effective doses of nemonapride virtually eliminated motor activity and induced severe catalepsy [2].
• The present study thus suggests that female patients with the A1 allele show a greater prolactin response to nemonapride, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia [3].
• Emonapride induced significant hyperthermia at high doses [4].
• Each D1 antagonist not only blocked typical sniffing and locomotor responses to RU 24213 but also released atypical myoclonic jerking behaviour, while the selective D2 antagonist YM 09151 blocked these typical responses but did not release jerking [5].

Psychiatry related information on nemonapride

• At 0.015 mg/kg, YM-09151-2 slightly augmented wakefulness, while at 1.0-2.0 mg/kg it significantly increased light sleep but depressed REM sleep [6].
• Pretreatment with YM-09151-2 in a dose which preferentially acts at presynaptic sites reversed the suppressant effects of a low dose of quinpirole on wakefulness and slow wave sleep [6].
• Similarly, YM-09151-2 (0.04 mg/kg, i.p.) antagonized apomorphine (0.125 mg/kg, s.c.)-induced stereotyped behavior in young chicks [7].
• The most frequently observed side effects during nemonapride treatment were extrapyramidal symptoms such as akathisia (69.7%), dystonia (48.5%), hypokinesia (45.5%), tremor (39.4%) and increased salivation (36.4%) [8].

High impact information on nemonapride

• The present results suggest that the Taq1 A DRD2 polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients, possibly by modifying the efficiency of DRD2 antagonism of the drug in the central nervous system [9].
• The relationship between dopamine D2 receptor polymorphism at the Taq1 A locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients [9].
• Therapeutic spectrum of nemonapride and its relationship with plasma concentrations of the drug and prolactin [10].
• The therapeutic spectrum of nemonapride, a new substituted benzamide, and its relationship with plasma concentrations of the drug and prolactin were investigated by a fixed-dose study (18 mg/day for 3 weeks) in 31 patients with acutely exacerbated schizophrenia [10].
• Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist [11].

Chemical compound and disease context of nemonapride

• Blockade of the dopamine D1 or D2 receptor with (+)-SCH 23390 (0.25 mg/kg s.c.) or YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide) (0.5 mg/kg s.c.), respectively antagonized the increase of waking and reduction of slow wave sleep induced by m-chloro-phenylbiguanide (10.0 micrograms) [12].
• Pretreatment with WAY 100635 (0.63 mg/kg) reinstated catalepsy at higher doses of nemonapride, indicating that the 5-HT1A receptor agonist properties of nemonapride are responsible for its inability to produce catalepsy at high doses [13].
• In this paper, the effects of three antipsychotic agents using the avian species laboratory model are described. d-Amphetamine (2-5 mg/kg, s.c.) dose-dependently antagonized catalepsy induced by haloperidol (0.25 mg/kg, i.p.), YM-09151-2 (0.02-0.04 mg/kg, i.p.) and (-)-sulpiride (20-40 mg/kg, i.p.) in rats [7].

Biological context of nemonapride

• Therefore, it is concluded that YM-09151-2 injected into the striatum produced a transient striatal DA release that is independent of D2 receptors and the action potential [14].
• The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain [15].
• The effects of different dopamine (DA) D2 receptor agonists and the DA D2 receptor antagonist, emonapride, on body temperature were studied in male mice [4].
• The substituted benzamide drugs YM 09151-2 and clebopride potently inhibited apomorphine-induced stereotyped behaviour in the rat and caused displacement of the specific binding of [3H]spiperone to D-2 binding sites on striatal membranes in low nanomolar concentrations [16].
• This method is applicable to drug level monitoring in the plasma of schizophrenia patients treated with nemonapride and to the study of pharmacokinetics [17].

Anatomical context of nemonapride

• Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not [15].
• In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex [15].
• Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja [15].
• The rank order potency of competition on [3H]YM-09151-2 binding by dopaminergic ligands in the hippocampus was YM-09151-2 > (+)-butaclamol > dopamine > sulpiride > SCH-23390; which shows the appropriate dopamine D2-like receptor profile [18].
• Experiments with cloned rat alpha1-adrenoceptor subtypes transiently expressed in COS cells confirmed the known selectivity of the investigated drugs for alpha1-adrenoceptor subtypes or the lack thereof of nemonapride [19].

Associations of nemonapride with other chemical compounds

• The effects of the selective dopamine D2 receptor antagonists YM-09151-2 and l-sulpiride on the in vivo release of dopamine (DA), L-3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat striatum were investigated [14].
• Pretreatment of rats with typical APD (haloperidol, 0.25-3 mg/kg; chlorpromazine, 5-10 mg/kg; cis-flupenthixol, 1 mg/kg; zotepine, 5 mg/kg; nemonapride, 0.5-2 mg/kg) potently reversed the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-induced D2 receptor inactivation in rat striatum [20].
• The actions in vitro of SCH 23390, YM 09151-2 and both enantiomers of 3-PPP on D-1 and D-2 dopamine receptors were investigated in superfused rat neostriatal slices [21].
• The present study suggests that Taq1 A polymorphism is not related to the development of extrapyramidal adverse effects during acute phase of bromperidol and nemonapride treatments [22].
• The affinity ratios of the ligands at 5-HT1A vs. D2 receptors also varied widely: ziprasidone, SSR181507 and SLV313 had similar affinities whereas aripiprazole, nemonapride and bifeprunox were more potent at D2 than 5-HT1A receptors [23].

Gene context of nemonapride

• In the present study, the relationship between this polymorphism and prolactin response to nemonapride, an antipsychotic drug with selective and potent DRD2 antagonistic property, was investigated in 25 Japanese schizophrenic inpatients (13 males, 12 females) [3].
• This inhibitory effect of SND 919 was blocked by concurrent application of a dopamine D-2 receptor antagonist, YM-09151-2 [24].
• After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared [15].
• Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels [25].
• However, topographical effects of 0.005 to 0.625 mg/kg YM 09151-2, namely, reduction in sniffing, locomotion, rearing, grooming, and chewing but not sifting, were essentially absent in DARPP-32 mutants [26].

Analytical, diagnostic and therapeutic context of nemonapride

• The microinjection of YM-09151-2 (10 microg), a D2 antagonist, into these regions could not stop SIB [27].
• The duration of the afterdischarge induced by electrical stimulation of the amygdaloid nucleus was initially shortened and thereafter prolonged by both YM-09151-2 and haloperidol [28].
• The D2 antagonist YM-09151-2 showed a similar profile, increasing cocaine self-administration at 0.01 and 0.016 mumol/kg, SC and suppressing responding by most animals at the dose of 0.03 mumol/kg, SC [29].
• cis-N-(1-Benzyl-2-methylpyrrolidine-3-yl)-5-iodo-2-methoxy-4-(methylamin o) benzamide (IYM), a YM-09151-2 analog iodinated at the 5-position of the benzoyl moiety, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain dopamine D2 receptors by single photon emission computer tomography (SPECT) [30].
• Dopamine antagonists, such as haloperidol (0.3-1 mg/kg IP), and nemonapride (0.3-1 mg/kg IP), reversed the dissociation between the cortical and hippocampal EEG in ketamine (60 mg/kg IP)-treated rats [31].

References