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  • Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

Die Pharmazie (2015-05-20)
Thanh Thao Nguyen, Hyun Ju Song, Sung Kwon Ko, Uy Dong Sohn
ABSTRACT

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Isoquinoline, 97%
Supelco
Ondansetron Hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Ondansetron hydrochloride, United States Pharmacopeia (USP) Reference Standard
Ondansetron for TLC system suitability, European Pharmacopoeia (EP) Reference Standard
Ondansetron for LC system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Ondansetron hydrochloride dihydrate, ≥98% (HPLC), powder
Ondansetron hydrochloride dihydrate, European Pharmacopoeia (EP) Reference Standard
USP
Atropine sulfate, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Methysergide maleate salt, solid
Sigma-Aldrich
Ketanserin (+)-tartrate salt, ≥97%, solid
Sigma-Aldrich
Serotonin creatinine sulfate monohydrate, powder
Sigma-Aldrich
Atropine sulfate salt monohydrate, ≥97% (TLC), crystalline
Supelco
Atropine Sulfate, Pharmaceutical Secondary Standard; Certified Reference Material
Atropine sulfate, European Pharmacopoeia (EP) Reference Standard