A novel water-soluble dopamine-2 antagonist with anticholinesterase activity in gastrointestinal motor activity

Iwanaga, Yuji; Miyashita, Naoshi; Morikawa, Kouji; Mizumoto, Akiyoshi; Kondo, Yoichi; Itoh, Zen

doi:10.1016/0016-5085(90)91022-x

Cited by 62 publications

(55 citation statements)

References 17 publications

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“…Itopride has antiacetylcholinesterase (AChE) activity as well as dopamine D 2 receptor antagonist activity and is used for the symptomatic treatment of functional dyspepsia (Iwanaga et al, 1990(Iwanaga et al, , 1994. It is well established that the M 3 receptor exists on the smooth muscle layer throughout the whole gut and that acetylcholine released from the enteric nerve endings stimulates the contraction of smooth muscle through the M 3 receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Although stimulation of gastrointestinal motility by itopride is ascribed to activation of the cholinergic drive based on D 2 receptor blocking and anti-AChE activity (Iwanaga et al, 1990(Iwanaga et al, , 1994, the stimulatory action on colonic motility seems mainly due to anti-AChE activity. Because gastrointestinal smooth muscle is directly stimulated by ACh through the activation of the M 3 receptor irrespective of the gastrointestinal site and animal species, it is apparent that itopride can stimulate colonic contractions as well as antral contractions in all species.…”

Section: Discussionmentioning

confidence: 99%

“…but tended to increase blood pressure and to suppress respiration (Kishibayashi et al, 1994). Also, dogs often collapsed when neostigmine was intravenously administered at 1000 g/kg (Iwanaga et al, 1990). Itopride did not cause any adverse effects such as salivation, snivel, vomiting, and diarrhea based on anti-AChE action throughout our experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Delayed gastric emptying is considered one of causes of functional dyspepsia. Itopride was reported to enhance gastric emptying in dogs, rats, and humans, and it stimulated canine gastrointestinal motility (Iwanaga et al, 1990Harasawa and Miwa, 1993). Mosapride was also reported to stimulate upper gastrointestinal motility in vivo and in vitro (Mine et al, 1997).…”

mentioning

confidence: 99%

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Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo

Tsubouchi

Saito²,

Mizutani³

et al. 2003

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo

Tsubouchi

Saito²,

Mizutani³

et al. 2003

J Pharmacol Exp Ther

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“…by inhibiting the action of dopamine on the D2 receptors on the post-synaptic cholinergic nerves and by stimulating the release of acetylcholine in the myenteric plexus. [7][8][9] It also prevents the hydrolysis of the released acetylcholine by the enzyme acetylcholinesterase. 7 Acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscles through M3 receptors throughout the gut.…”

mentioning

confidence: 99%

A randomised double blind trial to compare the efficacy and tolerability of itopride hydrochloride versus domperidone in patients with non-ulcer dyspepsia: bloating predominant type

Valoth

Kizhedath

2017

Int J Basic Clin Pharmacol

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Background: Non-ulcer dyspepsia is a treatment challenge due to multiple pathophysiological mechanisms and different symptoms. Several prokinetic drugs are tried without any unanimity regarding safety and efficacy. The objective of the study was to compare the efficacy and safety of Itopride and Domperidone in bloating predominant non ulcer dyspepsia patients.Methods: Patients were randomly assigned to two groups (20 each) to receive either 50mg of Itopride three times daily or 10mg of Domperidone three times daily. Only patients with predominant bloating were considered and their baseline symptoms recorded. The symptoms were graded on a 4-point scale - the Global Symptom Score scale and the patients were reassessed at the end of 2 and 4 weeks. The relief of symptoms was also assessed at the end of 2 and 4 weeks on a 5-point scale - The Patients’ Subjective Global Assessment of Relief scale.Results: Both the drugs significantly produced symptomatic relief. Though Domperidone is marginally beneficial compared to Itopride after 4 weeks treatment in terms of improvement in symptom scores, the Subjective Global Assessment of relief did not show any significant improvement between the two drugs.Conclusions: Treatment with Itopride was safe, well tolerated, resulted in good symptomatic relief, and was comparable in efficacy to Domperidone in relieving the symptoms of NUD. Hence it can be considered a good alternative for the treatment of non-ulcer dyspepsia.

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Design and Synthesis of Novel Dual Cholinesterase Inhibitors: In Vitro Inhibition Studies Supported with Molecular Docking

Koca

Güller

et al. 2022

Chemistry & Biodiversity

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The major cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are important in the therapy of Alzheimer's disease (AD) based on the cholinergic hypothesis. As a result, in recent years, the investigation of dual cholinesterase inhibition methods has become important among scientists. In this study, novel N‐(4‐chlorobenzyl)‐3,4‐dimethoxy‐N‐(m‐substituted)benzamide derivatives were synthesized. Then, inhibitory properties of these derivatives were examined in human AChE and BuChE in vitro and possible interactions were determined by molecular docking studies. All benzamide derivatives were exhibited dual inhibitory character and high BBB permeability. The most effective inhibitor was found as N7 for both AChE and BuChE with IC50 values of 1.57 and 2.85 μM, respectively. Besides the most potent inhibitor was predicted as N7 in terms of binding energies with −12.18 kcal/mol and −9.92 kcal/mol, respectively. The reason for these results is that bromine (N7) is the bulkiest molecule among the other substituted groups. These derivatives could be exploited to develop new medications for the treatment of central nervous system‐related diseases as AD by acting as dual inhibitors of AChE and BChE.

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A novel water-soluble dopamine-2 antagonist with anticholinesterase activity in gastrointestinal motor activity

Cited by 62 publications

References 17 publications

Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo

Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo

A randomised double blind trial to compare the efficacy and tolerability of itopride hydrochloride versus domperidone in patients with non-ulcer dyspepsia: bloating predominant type

Design and Synthesis of Novel Dual Cholinesterase Inhibitors: In Vitro Inhibition Studies Supported with Molecular Docking

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