ライフサイエンスコーパス: clozapine

1 nner, similar to the atypical antipsychotic, clozapine.

2 ty, such as omega-3 fatty acids, lithium and clozapine.

3 in patients with schizophrenia treated with clozapine.

4 nt-resistant schizophrenia do not respond to clozapine.

5 at baseline and 6-9 months after commencing clozapine.

6 1 by a QT prolonging drug: the antipsychotic clozapine.

7 in adult patients with schizophrenia taking clozapine.

8 ould enable safer and more widespread use of clozapine.

9 et for atypical antipsychotic drugs, such as clozapine.

10 enia who have not previously been exposed to clozapine.

11 mice treated for 21 days with haloperidol or clozapine.

12 , and inverse agonist and antipsychotic drug clozapine.

13 old) relative to the original pharmacophore, clozapine.

14 ance to the locomotor suppressive effects of clozapine.

15 ptor dimerization and the atypical nature of clozapine.

16 mediate the locomotor-suppressing effects of clozapine.

17 s from rats that were administered 2.5 mg/kg clozapine.

18 ditive or synergistic with the antipsychotic clozapine.

19 psychotics regarding self-harm compared with clozapine.

20 us lipid to normalize the signal response of clozapine.

21 r treatment with the atypical antipsychotic, clozapine.

22 r antipsychotic to switch to and when to use clozapine.

23 s showed decreased PPI which normalized with clozapine.

24 antipsychotic drug and for combinations with clozapine.

25 may underlie some of the clinical effects of clozapine.

26 posite for rapidly measuring serum levels of clozapine.

27 mide may be a key mediator of the effects of clozapine.

28 ght underlie the unique clinical efficacy of clozapine.

29 dol (1 mg/kg) and the atypical antipsychotic clozapine (20 mg/kg) increased BDNF levels by only 8-10%

30 doses of haloperidol (0.5 mg/kg, 1.0 mg/kg), clozapine (7.5 mg/kg, 10 mg/kg) or PD149163 (1.0 mg/kg,

31 However, clozapine administration partly antagonized the fall in

32 provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measurin

33 Clozapine also dramatically reduced locomotor activity,

34 Herein, we sought to determine whether clozapine also utilizes betaarrestin2-mediated mechanism

35 cell count is compulsory in patients taking clozapine, although the incidence of drug-induced agranu

36 festations were responsive to treatment with clozapine, an atypical antipsychotic drug.

37 Although effects of clozapine and haloperidol alone were relatively minor, t

38 were calculated for the scans in which both clozapine and IS were detected.

39 The anti-suicidal effects of clozapine and lithium have been substantiated, but might

40 Clozapine and long-acting injectable antipsychotic medic

41 etabolites in tissues is demonstrated, where clozapine and N-desmethylclozapine were observed from mo

42 like rat pheochromocytoma (PC-12) cell line, Clozapine and N-desmethylclozapine were tested for their

43 od was collected to assess concentrations of clozapine and NDMC as well as serum anticholinergic acti

44 t associations were found between individual clozapine and NDMC concentrations and working memory per

45 authors hypothesized that the ratio of serum clozapine and NDMC concentrations would be inversely ass

46 in schizophrenia, and antipsychotics such as clozapine and olanzapine have been associated with diffe

47 eport found no difference between effects of clozapine and olanzapine on cortical thickness.

48 this mechanism to the therapeutic effects of clozapine and olanzapine, both highly effective therapeu

49 scarinic action of the atypical neuroleptics clozapine and olanzapine.

50 eat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means to

51 campal slices treated with the antipsychotic clozapine and other more selective D4R antagonists.

52 Systemic clozapine and PD149163 but not haloperidol facilitated P

53 Atypical antipsychotic drugs, such as clozapine and risperidone, have a high affinity for the

54 e extent to which the atypical antipsychotic clozapine and the typical antipsychotic haloperidol coul

55 f morphine, codeine, oxymorphone, oxycodone, clozapine, and buspirone and their deuterated internal s

56 Our findings suggest that clozapine, and related centrally acting drugs, might be

57 A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy ou

58 knockout (KO) mice treated with haloperidol, clozapine, and risperidone were assessed for locomotor a

59 tment in patients unlikely to respond to non-clozapine antipsychotics.

60 tions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects i

61 We conclude that clozapine appears to affect the development and induce l

62 ies of antipsychotics including haloperidol, clozapine, aripiprazole, chlorpromazine, quetiapine, ola

63 nt use includes the protypical atypical APD, clozapine, as well as aripiprazole, asenapine, iloperido

64 get of atypical antipsychotic drugs, notably clozapine, as well as some other psychotropic agents.

65 We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases

66 Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2-/-.

67 ng white blood cell count in patients taking clozapine, based on divergent national requirements, do

68 Our data show that clozapine binding to Kv11.1 is complex.

69 an describe the observed kinetic features of clozapine block and correctly predict the overall affini

70 n 2.5 hours while agonist DOI and antagonist clozapine bring about recycling in 7.5 hours.

71 Only four ligands (5-HT, DA, DOI, and clozapine) bring about receptor endocytosis.

72 Such hyperactivity was ameliorated by clozapine but not haloperidol or ziprasidone.

73 on Gadd45-beta was mimicked by valproate and clozapine but not haloperidol.

74 We further observed that clozapine clears protein aggregates, such as alpha-synuc

75 nical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research di

76 Clinically relevant doses of clozapine (CLZ) (3.8 to 15 micromol/kg twice a day s.c.

77 P), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ), at concentrations typical of high thera

78 dequately informed patients, the Netherlands Clozapine Collaboration Group now permits quarterly moni

79 ent-resistant schizophrenia not treated with clozapine compared with clozapine-treated individuals.

80 evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsycho

81 rovide little evidence of the superiority of clozapine compared with other second-generation antipsyc

82 duced sensitivity to the sedating effects of clozapine compared with wild-type (WT) littermates, para

83 c activity was significantly associated with clozapine concentration, but not with working memory per

84 H(2)O(2) vs. PC-12 cells, and explaining why Clozapine could not protect these cells.

85 elevated BDNF levels in the amygdala, while clozapine decreased BDNF in the olfactory bulb.

86 We also demonstrate that clozapine decreases locomotor activity in a 5-HT(2A)-dep

87 osomal incubations, including acetaminophen, clozapine, diclofenac, imipramine, meclofenamic acid, an

88 hotic drug treatment, including the atypical clozapine, did not affect Hdac1 levels in PFC but induce

89 n of three series of homobivalent ligands of clozapine, differing in the length and nature of the spa

90 ess mortality was observed in the year after clozapine discontinuation (hazard ratio: 2.65, 95% CI: 1

91 t extent the observed excess mortality after clozapine discontinuation is confounded by nonadherence

92 in physical or mental health precipitated by clozapine discontinuation.

93 Clozapine dosages remained constant.

94 A low clozapine dose (1 mg/kg intravenous) significantly count

95 Clozapine dose-dependently attenuated the absolute S-(+)

96 use L-745,870 and the atypical antipsychotic clozapine dramatically reduce the NRG-1-induced increase

97 alantamine, modafinil, levodopa, rotigotine, clozapine, duloxetine, clonazepam, ramelteon, gabapentin

98 ine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group).

99 granulocytosis is rare during treatment with clozapine, especially in monotherapy.

100 dopamine receptor antagonists (haloperidol, clozapine, eticlopride, and SCH23390).

101 t is mediated by adverse effects from recent clozapine exposure or deterioration in physical or menta

102 xamined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia.

103 Quantitation of clozapine from the brain, lung, kidney, and testis, by u

104 None of the patients in the clozapine group met the criterion.

105 Nonresponders from the clozapine group received an 8-week open trial of ECT (cr

106 All 19 patients from the clozapine group received ECT in the crossover phase.

107 phrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus cloza

108 se of bilateral ECT plus clozapine (ECT plus clozapine group).

109 articipants (ECT plus clozapine group, N=20; clozapine group, N=19).

110 at sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19).

111 were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone.

112 Pharmacological augmentation to clozapine has been studied with unimpressive results.

113 her for nonclozapine antipsychotics than for clozapine (hazard ratio: 1.36, 95% CI: 1.04-1.78).

114 not receiving clozapine than for those given clozapine (hazard ratio: 1.88, 95% confidence interval [

115 uclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting inj

116 Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-act

117 led by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner.

118 We studied behavioral effects of clozapine in Caenorhabditis elegans to identify novel pa

119 cations from DESI-MSI revealed 0.2-1.2 ng of clozapine in individual brain sections, results that wer

120 are, lithium for mood-disordered adults, and clozapine in schizophrenia.

121 Patients treated with clozapine in the efficacy pathway made comparable gains.

122 nstated the locomotor-suppressing effects of clozapine in the open field.

123 nd labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hype

124 Clozapine increased prepulse inhibition (PPI) in wild-ty

125 Both haloperidol and clozapine increased the levels of GAD(67) in the cerebel

126 In contrast, clozapine induced a marked and immediate reversal of MDM

127 riants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163

128 tion but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG

129 s genome-wide RNAi screen for suppressors of clozapine-induced developmental delay and lethality reve

130 ay explain the role of the gene in mediating clozapine-induced developmental delay/lethality.

131 e of D2-like signaling is not sufficient for clozapine-induced histone methylation.

132 Specifically, we found that clozapine-induced increase in egg laying requires tyrami

133 xamined pharyngeal pumping and observed that clozapine-induced inhibition of pharyngeal pumping requi

134 in TAAR1 knockout mice, implicating TAAR1 in clozapine-induced PPI enhancement.

135 ophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophr

136 essed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated

137 Clozapine is a particularly effective antipsychotic medi

138 Clozapine is an antipsychotic medication with superior e

139 In treatment-resistant schizophrenia, clozapine is considered the standard treatment.

140 ism are effective for motor fluctuations and clozapine is effective for hallucinations.

141 Although clozapine is known to inhibit 5-HT2AR signaling through

142 (APD), clozapine, is of great importance, as clozapine is more effective and has therapeutic benefits

143 Clozapine is one of the most promising medications for m

144 Clozapine is unique among the atypical APDs in its effic

145 The antipsychotic clozapine is uniquely effective in the management of sch

146 Increasing the judicious use of clozapine is warranted together with vigilance to preven

147 s of action of the antipsychotic drug (APD), clozapine, is of great importance, as clozapine is more

148 Timely measurement of serum clozapine levels has been identified as a barrier to the

149 haloperidol (Sprague-Dawley rats [N=16]) or clozapine (Long-Evans rats [N=20]).

150 implicate biological pathways through which clozapine may act to cause this serious adverse effect.

151 In this regard, clozapine may also be considered a functionally selectiv

152 Despite evidence that clozapine may be neuroprotective, there are few longitud

153 and rapid electrochemical approach for serum clozapine measurements should provide clinicians with th

154 We demonstrate that unlike serotonin, clozapine-mediated 5-HT2AR internalization and Akt phosp

155 fore-unknown role for trace amine systems in clozapine-mediated effects across two species: C. elegan

156 ed receptor endocytosis, but DA-mediated and clozapine-mediated internalization is not affected if PK

157 Moreover, clozapine-mediated suppression of MK-801 and phencyclidi

158 1,3-dihydro-2H-benzimidazol-2-one) , and the clozapine metabolite N-desmethylclozapine.

159 With buspirone and clozapine metabolites in human plasma as examples, this

160 ectrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement ( approx

161 schizoaffective disorder who were receiving clozapine monotherapy at bedtime completed the MATRICS C

162 is that emerged after 19 years of continuous clozapine monotherapy.

163 Among multiple actions of clozapine, muscarinic acetylcholine (ACh) activation mar

164 g intracranial or systemic administration of clozapine N-oxide (CNO) and tested the ability of system

165 Males received clozapine N-oxide (CNO) or vehicle injections before eac

166 mporally by the administration of the ligand clozapine N-oxide (CNO).

167 exclusively activated by the "designer drug" clozapine N-oxide (CNO).

168 Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and

169 a concurrent gain in potency for the ligand clozapine N-oxide.

170 althy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line ant

171 dence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched co

172 Western blots revealed that Clozapine, N-desmethylclozapine, and DETC reduce the pho

173 Cumulatively, these results indicate that Clozapine, N-desmethylclozapine, DETC, and U0126 protect

174 nergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated

175 Administering clozapine-N-oxide (CNO) enabled precise DREADD-dependent

176 coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca(

177 d and subsequently activated by their ligand Clozapine-N-oxide (CNO) in conjunction with fear extinct

178 adora2A-rM3Ds mouse, activation of rM3Ds by clozapine-N-oxide (CNO) induces DARPP-32 phosphorylation

179 nd after administration of the DREADD ligand clozapine-N-oxide (CNO) or vehicle (saline).

180 und that activation of hM(4)D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron

181 ce expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h incre

182 er injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and un

183 ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically

184 Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1

185 tion to a bioinert drug-like small molecule, clozapine-N-oxide (CNO).

186 ons could be dose-dependently inactivated by clozapine-n-oxide (CNO).

187 lencer in the presence of its cognate ligand clozapine-N-oxide (CNO).

188 lly inactive and orally bioavailable agonist clozapine-N-oxide (CNO).

189 ated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO).

190 acologically inert, orally bioavailable drug clozapine-N-oxide (CNO).

191 ated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO).

192 idal neurons and activated the receptor with clozapine-N-oxide (CNO).

193 d AAV-hSYN-eYFP vector that was treated with clozapine-N-oxide (CNO; 3 mg/kg, i.p.) before stage II s

194 otherwise pharmacologically inert compound (clozapine-N-oxide), leading to the conditional activatio

195 y inert drug-like and bioavailable compound (clozapine-N-oxide).

196 was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transientl

197 M3D-arr using the otherwise inert compound, clozapine-N-oxide, we found that M3D-arr activation incr

198 Likewise, clozapine-N-oxide-induced inhibition of PV interneurons

199 us administration of the inert DREADD ligand clozapine-N-oxide.

200 cologically inert, but bioavailable, ligand (clozapine-N-oxide; CNO), while being non-responsive to e

201 This finding suggests that manipulating the clozapine/NDMC ratio could enhance cognition in patients

202 This hypothesis-driven study confirms that clozapine/NDMC ratio is a strong predictor of working me

203 The clozapine/NDMC ratio was significantly and negatively as

204 Like clozapine, olanzapine acts via alpha7 nicotinic receptor

205 Some second-generation antipsychotics (eg, clozapine, olanzapine, quetiapine, and risperidone) are

206 bility assay detected a protective effect of Clozapine on human embryonic kidney (HEK293), rat primar

207 The dissociable effects of haloperidol and clozapine on ketamine-induced hyperoxygenation and mPFC-

208 dditionally, studies examining the effect of clozapine on the brain can help to identify aspects of c

209 Drug effects (PCP followed by clozapine) on the activity of RtN (single unit and local

210 tiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with

211 Interventions were new initiation of clozapine or a standard antipsychotic medication, define

212 erence in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole,increased i

213 tide-1 receptor agonist liraglutide added to clozapine or olanzapine treatment of schizophrenia spect

214 Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and h

215 chizophrenia spectrum disorders treated with clozapine or olanzapine.

216 No combination strategies with clozapine outperformed controls.

217 of acetaminophen, diclofenac, carbamazepine, clozapine, p-cresol, 4-ethylphenol, and 3-methylindole i

218 Fifty percent of the ECT plus clozapine patients met the response criterion.

219 mining clinical and functional outcomes with clozapine positioned as a second-line treatment.

220 en studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to

221 studies have shown that atypical APDs (e.g., clozapine) preferentially increases dopamine (DA) and ac

222 f rare variants to treatment response, using clozapine prescription as a proxy for treatment resistan

223 olicy makers in the revision of guidance for clozapine prescription.

224 with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-2

225 Acute administration of clozapine rapidly increased extracellular dopamine level

226 Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central

227 Clozapine represents the best-characterized atypical ant

228 zed single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treat

229 previous suggestive evidence of an impact on clozapine response in patients with schizophrenia, we co

230 ne, as well as the prototypical atypical APD clozapine, restored NMDAR-mediated synaptic responses to

231 trast to the leading theory that sedation by clozapine results from anti-histaminergic effects, we sh

232 However, clozapine reversal of PCP effects is not driven by resto

233 Treatment with the antipsychotic drug clozapine reverses the behavioral and spine defects.

234 tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%).

235 of atypical antipsychotic drugs (APDs), e.g. clozapine, risperidone, olanzapine and ziprasidone, to i

236 Although betaarrestin2 has no effect on clozapine's actions in vivo, Akt phosphorylation is requ

237 xplored whether trace amine systems modulate clozapine's behavioral effects in mammals by studying tr

238 ans to identify novel pathways that modulate clozapine's biological effects.

239 in vivo, Akt phosphorylation is required for clozapine's efficacy in blocking MK-801- and PCP-induced

240 idol and risperidone, but did not respond to clozapine's locomotor-suppressing effects.

241 Clozapine's potent antagonism of muscarinic M1 receptors

242 rate to second-line treatments, coupled with clozapine's substantial response rate in refractory schi

243 The molecular basis of clozapine's therapeutic profile is not well understood.

244 We found that patients treated with clozapine show lower dopamine synthesis capacity than pa

245 Clozapine shows greater efficacy in children and adolesc

246 ntified signaling pathways that mediate this clozapine-specific effect on egg laying.

247 This effect was clozapine-specific, as it was not observed with exposure

248 Clozapine stimulated egg laying in C. elegans in a dose-

249 Future clozapine studies with high doses and patients with extr

250 national registries of patients treated with clozapine, study cohorts, and a pharmacovigilance databa

251 tipsychotic effects of either haloperidol or clozapine, suggesting that these compounds mediate their

252 ry drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxif

253 tality was higher for patients not receiving clozapine than for those given clozapine (hazard ratio:

254 on the brain can help to identify aspects of clozapine that make it uniquely effective in patients wi

255 As demonstrated with the antipsychotic drug clozapine, the DTome tool was effective and promising fo

256 ound that sensory inhibition was improved by clozapine, the prototypical atypical antipsychotic, but

257 Clozapine, the treatment of choice in refractory schizop

258 We treated BN rats with haloperidol or clozapine to determine if the BN rat is a useful animal

259 Clozapine, to which CNO rapidly converts in vivo, shows

260 chemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia

261 neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide associ

262 nia not treated with clozapine compared with clozapine-treated individuals.

263 lored an association between commencement of clozapine treatment for schizophrenia and changes in reg

264 mortality and self-harm in association with clozapine treatment in individuals with treatment-resist

265 clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to n

266 Clozapine treatment led to reductions in caudate nucleus

267 or that it is contributed to by switching to clozapine treatment.

268 ients with schizophrenia who are switched to clozapine treatment.

269 rrently showed low symptom severity with the clozapine treatment.

270 terly monitoring after the first 6 months of clozapine treatment.

271 blood cell counts that are now required for clozapine treatment.

272 ts or longitudinally assessed the effects of clozapine treatment.

273 in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correl

274 However, clozapine use has restrictions owing to its many adverse

275 Practical issues related to clozapine use, in combination with the robust response r

276 sition LC/MS/MS of the MH(+) ion of the drug clozapine, using the same solvent flow rate, produced a

277 ogically oppositional ligands, serotonin and clozapine, utilize differential mechanisms to achieve th

278 -1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ra

279 sed incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ra

280 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ra

281 Initiation of clozapine was associated with a significantly decreased

282 Clozapine was associated with more overall adverse event

283 Clozapine was associated with significantly increased in

284 The presence of clozapine was detected in all tissue types, whereas the

285 Clozapine was included for patients who chose this pathw

286 Clozapine was localized and quantified in individual bra

287 The improvement after clozapine was mediated by alpha7 nicotinic receptors.

288 13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0

289 The most surprising finding was that clozapine was not significantly better than most other d

290 ychotic drug and 5 strategies that augmented clozapine were examined.

291 r the readily detected uric acid and for the clozapine which is present at 100-fold lower concentrati

292 dentified as a barrier to the broader use of clozapine, which is however challenging due to the compl

293 Antipsychotic drugs haloperidol and clozapine, which target monoamine receptors, as well as

294 The augmentation of clozapine with ECT is a safe and effective treatment opt

295 d apparent nonstate-dependent interaction of clozapine with Kv11.1.

296 be a case of serotonin syndrome secondary to clozapine withdrawal and concomitant use of citalopram h

297 s of serotonin syndrome attributed to abrupt clozapine withdrawal with concomitant use of citalopram.

298 ainly call into question the likelihood that clozapine would be chosen if it were an option at this s

299 This raises the question of whether clozapine would be more effectively positioned as a firs

300 achment of the spacer at the N4' position of clozapine yielded a series of homobivalent ligands that