Comparison of the Effects of Pantethine and Fursultiamine on Plasma Gastrointestinal Peptide Levels in Healthy Volunteers

Abstract

Postoperative ileus following laparotomy is a common complication after abdominal surgery and involves the delay of bowel transit caused by impaired motility. Pantethine is the stable disulfate form of pantetheine, the metabolic substrate that constitutes the active moiety of CoA molecule and acyl carrier proteins. Pantethine is known to increase gastrointestinal motility and improve ileal function. 1) A part of the contractile mechanism is thought to be mediated by acetylcholine release from the cholinergic nerve endings. 2) Fursultiamine hydrochloride (fursultiamine), a vitamin B 1 derivative, is also reported to enhance gastrointestinal motility by the effect on enteric hyperponetic neuron. 3,4) Therefore, pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. 1,5) In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. [6][7][8] Calcitonin gene-related peptide (CGRP) is known to inhibit acid secretion and stimulate mucosal blood flow. 9) Vasoactive intestinal polypeptide (VIP) has vasodilating effect, and is an important neurotransmitter for the enteric nervous system. 10) Motilin has powerful fundic pouch motor-stimulating activity, and is one of the most important factors that control the occurrence of regular contractions (phase 3) of the migrating motor complex. 11) Substance P (SP) coexists with CGRP in the sensory afferent neurons of the gastrointestinal mucosa. 12) Some drugs used to treat postoperative ileus are known to affect the gastrointestinal peptide levels in humans. Dai-kenchu-to and Ninjin-to, the traditional herbal medicines used to treat postoperative ileus, have been shown to raise CGRP and SP levels in human plasma. 13,14) The effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in humans have not been demonstrated. Therefore, we examined the effects of these two compounds on plasma levels of CGRP-, VIP-, motilin-and SP-like immunoreactive substances (IS) in healthy subjects. MATERIALS AND METHODSMaterials Pantethine (Pantosin tablet) was purchased from Daiichi Sankyo Co., Ltd. (Tokyo, Japan). Fursultiamine (Alinamin-F sugar-coated tablet) was purchased from Takeda Pharmaceutical Co., Ltd. (Osaka, Japan). Maize starch (Wako Pure Chemicals Co., Ltd., Osaka, Japan) was used as placebo. Synthetic human CGRP and its fragment (8-37), VIP, motilin and SP were purchased from Peptide Institute, Inc. (Osaka, Japan). VIP fragment (11-28) was supplied by Professor H. Yajima (Kyoto University, Kyoto, Japan). Antiserum to CGRP (14160) was purchased from Peptide Institute, Inc. (Osaka, Japan), VIP (T-4116) from Peninsula Laboratories (California, U.S.A.), and motilin (Y121) and SP (Y150) from Yanaihara Institute (Shizuoka, Japan). All other reagents were analytical reagent grade from commercial sources.Subjects Five healthy male nonsmoking ...

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“…The lower detection limit for SP was 0.32 pg mL -1 , as calculated from the fluorescence intensity at three-times the standard deviation of the fluorescence intensity in the absence of SP. The lower detection limit was comparable to that (0.25 pg mL -1 ) of the competitive fluorometric immunoassay, 34 but it was much superior to those of the liposome array method (sub-pg mL -1 ), 31 as well as the radioimmunoassay (10 -20 pg mL -1 ), 35,36 the solid-phase immobilized epitope immunoassay (6 pg mL -1 ) 37 and the amperometric micro-immunosensor (10 pg mL -1 ). 18 …”

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“…The lower detection limit is comparable to that (0.25 pg mL -1 ) of the competitive fluorometric immunoassay, 54 but it is much superior to those of the liposome array method (sub-pg mL -1 ), 35 the radioimmunoassay (10 -20 pg mL -1 ), 55,56 the solid-phase immobilized epitope immunoassay (6 pg mL -1 ) 57 and amperometric microimmunosensor (10 pg mL -1 ). 58…”

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“…Oxiglutatione, a disulfide peptide dimer, is prescribed for breast cancer therapy and the treatment for chronic obstructive pulmonary diseases. 36 Fursultiamine is used for vitamin-related disorders, 37 while lipoic acid is employed for the treatment of hearing loss, diabetic neuropathy, multiple sclerosis, and biocefalin cognition disorders. 38 Biocefalin is used to increase the cerebral brain activity in patients with impaired cerebral function, 39 and Pantethine, anticataract agents, is prescribed for the treatment of lipoprotein and vitamin-related disorders.…”