Mechanism of action of domperidone.ppt

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Mechanism of action of domperidone.ppt

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(1985) pKa 7.9 EL TAYAR, N ET AL. (1985) Predicted Properties Source Water Solubility 0.0925 mg/mL ALOGPS logP 3.7 ALOGPS logP 2.9 ChemAxon logS -3.7 ALOGPS pKa (Strongest Acidic) 12.52 ChemAxon pKa (Strongest Basic) 7.03 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon. The DA2-receptor antagonist domperidone antagonizes the inhibitory effect of dopamine, resulting in stimulation of gastric muscle contraction. This provides a mechanism for the gastrokinetic effect of domperidone. PMID : 1860634 PubMed - indexed for MEDLINE.

Tetrodotoxin abolished 3Hacetylcholine release evoked by veratridine, but hexamethonium had no effect. Domperidone, but not SCH 23390, antagonized the inhibitory action of dopamine. Pretreatment with pertussis toxin blocked the action of dopamine to inhibit evoked release of 3Hacetylcholine.

Abstract To test the hypothesis that domperidone stimulates gastric muscle contraction by antagonizing the inhibitory effects of dopamine on postsynaptic cholinergic neurons in the myenteric plexus, the effects of dopamine on circular muscle from the body of the guinea pig stomach were examined.

Schild analysis showed a Ki of 3 x 10(-8) mol/L and a slope of unity. In addition, it was shown that dopamine inhibited veratridine-evoked release of 3Hacetylcholine from the gastric myenteric plexus in a dose-related manner (median effective dose, 5.2 x 10(-5) mol/L).

Dopamine inhibited circular muscle contraction evoked by electric field stimulation in a dose-related manner. The threshold dose was 10(-6) mol/L and half-maximal inhibition occurred at 10(-5) mol/L. Preincubation of muscle contraction with atropine or tetrodotoxin abolished the contractile response to electric field stimulation, indicating mediation.

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The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure.

Antiemetic: The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D2 and D3 dopamine receptors, which are found in the chemoreceptor trigger zone, located.

Affected organisms Humans and other mammals Pathways Not Available SNP Mediated Effects Not Available SNP Mediated Adverse Drug Reactions Not Available ADMET Predicted ADMET features Property Value Probability Human Intestinal Absorption 0.9967 Blood Brain Barrier 0.8686 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.7029 P-glycoprotein.

Pricing information is supplied for informational purposes only. Patents Not Available Properties State Solid Experimental Properties Source melting point 242.5 C Vanderberk, J., Kennis, L.E.J., Van der Aa, M.J.M.C. and Van Heertum, A.H.M.T.; U.S.

Publication Types, MeSH Terms, Substances, Grant Support. Publication Types Research Support, U.S. Gov't, P.H.S. MeSH Terms Animals Domperidone/pharmacology Dose-Response Relationship, Drug. Gastric Emptying/drug effects Gastrointestinal Motility/drug effects Guinea Pigs. In Vitro Techniques Male Muscle Contraction/drug effects Muscle, Smooth/drug effects.

Identification Name Domperidone Accession Number DB01184 (APRD 00418) Type. Small Molecule Groups Approved, Investigational, Vet Approved Description. A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.

Abstract Send to: See comment in PubMed Commons below. Gastroenterology. 1991 Sep;101(3 703-10. Takahashi T 1, Kurosawa S, Wiley JW, Owyang C. Author information 1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.

These observations indicate that dopamine inhibits gastric muscle contraction evoked by electric field stimulation by inhibiting cholinergic transmission. This is mediated by DA2 receptors located on the postganglionic cholinergic neurons, and the pathway involves a pertussis toxin-sensitive G protein.