Ameliorative effect of chlorpromazine hydrochloride on visceral hypersensitivity in rats : possible involvement of 5-HT2A receptor
© 2017 The British Pharmacological Society..
BACKGROUND AND PURPOSE: Visceral hypersensitivity is responsible for pathogenesis of irritable bowel syndrome (IBS). Therefore, its prevention can help avoid abdominal pain and discomfort in IBS. To find candidate drugs for visceral hypersensitivity, we screened existing medicines for their ability to prevent visceral sensitivity induced by colorectal distension (CRD) in rats and identified chlorpromazine, a typical antipsychotic drug, as a candidate compound. In this study, we investigated the effect of chlorpromazine on visceral hypersensitivity.
EXPERIMENTAL APPROACH: Visceral sensitivity (visceromotor response) was monitored by measuring the electrical activity of the abdominal external oblique muscle contraction in response to CRD using a barostat apparatus. Visceral hypersensitivity was induced by a colonic instillation of sodium butyrate or acetic acid in neonates.
KEY RESULTS: Oral administration of chlorpromazine suppressed butyrate-induced visceral hypersensitivity to CRD. Interestingly, atypical antipsychotic drugs, quetiapine and risperidone, ameliorated butyrate-induced visceral hypersensitivity, whereas the typical antipsychotic drugs, haloperidol and sulpiride, did not. Pharmacological analysis using specific inhibitors showed that a selective 5-HT2A receptor antagonist, ketanserin, suppressed butyrate-induced visceral hypersensitivity, whereas a selective dopamine D2 receptor antagonist, L-741626, did not. Furthermore, the 5-HT2A receptor agonist AL-34662 stimulated visceral sensitivity to CRD in healthy control rats but not in butyrate-treated rats. These findings suggest that increased 5-HT levels in the colon contribute to the induction of visceral hypersensitivity.
CONCLUSIONS AND IMPLICATIONS: Our results indicate that chlorpromazine ameliorates visceral hypersensitivity and that the 5-HT2A receptor is a potential therapeutic target for treating abdominal pain and discomfort in IBS.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:174 |
|---|---|
| Enthalten in: |
British journal of pharmacology - 174(2017), 19 vom: 09. Okt., Seite 3370-3381 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Asano, Teita [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
107-92-6 |
|---|
| Anmerkungen: |
Date Completed 22.05.2018 Date Revised 09.01.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/bph.13960 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM274246392 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM274246392 | ||
| 003 | DE-627 | ||
| 005 | 20231225003044.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/bph.13960 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0914.xml |
| 035 | |a (DE-627)NLM274246392 | ||
| 035 | |a (NLM)28750135 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Asano, Teita |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ameliorative effect of chlorpromazine hydrochloride on visceral hypersensitivity in rats |b possible involvement of 5-HT2A receptor |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.05.2018 | ||
| 500 | |a Date Revised 09.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2017 The British Pharmacological Society. | ||
| 520 | |a BACKGROUND AND PURPOSE: Visceral hypersensitivity is responsible for pathogenesis of irritable bowel syndrome (IBS). Therefore, its prevention can help avoid abdominal pain and discomfort in IBS. To find candidate drugs for visceral hypersensitivity, we screened existing medicines for their ability to prevent visceral sensitivity induced by colorectal distension (CRD) in rats and identified chlorpromazine, a typical antipsychotic drug, as a candidate compound. In this study, we investigated the effect of chlorpromazine on visceral hypersensitivity | ||
| 520 | |a EXPERIMENTAL APPROACH: Visceral sensitivity (visceromotor response) was monitored by measuring the electrical activity of the abdominal external oblique muscle contraction in response to CRD using a barostat apparatus. Visceral hypersensitivity was induced by a colonic instillation of sodium butyrate or acetic acid in neonates | ||
| 520 | |a KEY RESULTS: Oral administration of chlorpromazine suppressed butyrate-induced visceral hypersensitivity to CRD. Interestingly, atypical antipsychotic drugs, quetiapine and risperidone, ameliorated butyrate-induced visceral hypersensitivity, whereas the typical antipsychotic drugs, haloperidol and sulpiride, did not. Pharmacological analysis using specific inhibitors showed that a selective 5-HT2A receptor antagonist, ketanserin, suppressed butyrate-induced visceral hypersensitivity, whereas a selective dopamine D2 receptor antagonist, L-741626, did not. Furthermore, the 5-HT2A receptor agonist AL-34662 stimulated visceral sensitivity to CRD in healthy control rats but not in butyrate-treated rats. These findings suggest that increased 5-HT levels in the colon contribute to the induction of visceral hypersensitivity | ||
| 520 | |a CONCLUSIONS AND IMPLICATIONS: Our results indicate that chlorpromazine ameliorates visceral hypersensitivity and that the 5-HT2A receptor is a potential therapeutic target for treating abdominal pain and discomfort in IBS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antipsychotic Agents |2 NLM | |
| 650 | 7 | |a Receptor, Serotonin, 5-HT2A |2 NLM | |
| 650 | 7 | |a Serotonin 5-HT2 Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Butyric Acid |2 NLM | |
| 650 | 7 | |a 107-92-6 |2 NLM | |
| 650 | 7 | |a Serotonin |2 NLM | |
| 650 | 7 | |a 333DO1RDJY |2 NLM | |
| 650 | 7 | |a Acetic Acid |2 NLM | |
| 650 | 7 | |a Q40Q9N063P |2 NLM | |
| 650 | 7 | |a Chlorpromazine |2 NLM | |
| 650 | 7 | |a U42B7VYA4P |2 NLM | |
| 700 | 1 | |a Tanaka, Ken-Ichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Tada, Arisa |e verfasserin |4 aut | |
| 700 | 1 | |a Shimamura, Hikaru |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Rikako |e verfasserin |4 aut | |
| 700 | 1 | |a Maruoka, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Mizushima, Tohru |e verfasserin |4 aut | |
| 700 | 1 | |a Takenaga, Mitsuko |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of pharmacology |d 1968 |g 174(2017), 19 vom: 09. Okt., Seite 3370-3381 |w (DE-627)NLM000001325 |x 1476-5381 |7 nnns |
| 773 | 1 | 8 | |g volume:174 |g year:2017 |g number:19 |g day:09 |g month:10 |g pages:3370-3381 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/bph.13960 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 174 |j 2017 |e 19 |b 09 |c 10 |h 3370-3381 | ||