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Neville A. Mcbrien - One of the best experts on this subject based on the ideXlab platform.
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The Mx Muscarinic Antagonist Pirenzepine Reduces Myopia and Eye Enlargement in the Tree Shrew
2013Co-Authors: Charles L. Cottriall, Neville A. McbrienAbstract:Purpose. To determine the efficacy of the Mi-selective muscarinic antagonist, Pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Methods. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either Pirenzepine (17.7 fimol; re = 9) or vehicle control (re = 6). Control groups (re = 6) were used to assess the effects of MD, injection regimen, and drug effects. Results. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced —13.2 D ± 0.8 D and —14.1 D ± 0.5 D of axial myopia, respectively. In Pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only —2.1 D ± 1.4 D. The significant reduction in myopia in Pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm ± 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm ± 0.02 mm and 0.29 mm ± 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in Pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia
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the effect of Pirenzepine on positive and negative lens induced refractive error and ocular growth in chicks
Investigative Ophthalmology & Visual Science, 2010Co-Authors: Sangeetha Metlapally, Neville A. McbrienAbstract:PURPOSE The selective muscarinic antagonist Pirenzepine inhibits experimentally induced myopia in avian and mammalian species, including nonhuman primates and adolescent humans. Transient positive lens defocus has a potent inhibitory effect on negative-lens-induced myopia in avian and mammalian models. The purpose of the present study was to determine the influence of daily treatment with Pirenzepine on ocular growth and refractive error in chicks wearing positive lenses. METHODS The chicks were allocated to one of eight groups (n = 6 each group) on the basis of whether they wore +10 or -10 D lenses monocularly and whether they received daily intravitreal injections of Pirenzepine (700 μg) or vehicle (phosphate-buffered saline) in the lens-defocused eye. In vivo refractive and biometric data were collected, and glycosaminoglycan synthesis in the sclera was assessed. RESULTS Pirenzepine did not alter the level of positive-lens-induced hyperopia in chicks wearing +10 D lenses compared with that in the vehicle control group (+8.1 ± 0.6 D vs. +8.9 ± 2.4 D, mean ± SEM; P = 0.76). In contrast, Pirenzepine caused significant inhibition of negative-lens-induced myopia compared with that in the vehicle group (-1.1 ± 1.5 D vs. -8.8 ± 1.1 D; P = 0.001). Glycosaminoglycan synthesis in the posterior sclera was significantly increased in the negative-lens-treated groups and showed small decreases in the positive-lens-treated groups. CONCLUSIONS The influence of Pirenzepine on ocular growth in chicks differed by sign of lens defocus, with Pirenzepine blocking negative-lens effects on ocular growth, but not positive-lens effects. The most likely reason that hyperopia was not enhanced by Pirenzepine treatment was that the rapid compensatory eye growth associated with positive lenses eliminated the imposed myopic defocus, and the clear retinal image prevented any additional hyperopia from developing.
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prevention of form deprivation myopia with Pirenzepine a study of drug delivery and distribution
Ophthalmic and Physiological Optics, 1999Co-Authors: Charles L. Cottriall, Neville A. Mcbrien, R Annies, E.m. LeechAbstract:Abstract The present study investigated the drug distribution and elimination profiles in ocular tissues of Pirenzepine, a selective M 1 muscarinic antagonist known to inhibit myopia. Results demonstrate that (1) Intravitreal injections of the M 1 selective antagonist Pirenzepine were more effective at preventing form-deprivation myopia than subconjunctival injections. (2) Maximum drug levels were reached within 1 hr for both retina and sclera following intravitreal (28 and 11 nanomole) and subconjunctival (0.25 and 1 nanomole) injection. Intravitreal injection proved a more effective route of drug delivery to all ocular tissues compared to subconjunctival injection. (3) Elimination times of Pirenzepine from ocular tissues were much shorter than those reported for blood plasma. (4) Histological examination revealed no evidence of gross toxic effects at doses effective in inhibiting induced axial myopia. In conclusion, Pirenzepine was effective at reducing form-deprivation myopia in a dose-dependent manner with no evidence of disruption to the retina. However, results were not conclusive as to where Pirenzepine may have its site of action in preventing form-deprivation myopia.
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The M1 muscarinic antagonist Pirenzepine reduces myopia and eye enlargement in the tree shrew.
Investigative ophthalmology & visual science, 1996Co-Authors: Charles L. Cottriall, Neville A. McbrienAbstract:Purpose. To determine the efficacy of the Mi-selective muscarinic antagonist, Pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Methods. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either Pirenzepine (17.7 fimol; re = 9) or vehicle control (re = 6). Control groups (re = 6) were used to assess the effects of MD, injection regimen, and drug effects. Results. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced —13.2 D ± 0.8 D and —14.1 D ± 0.5 D of axial myopia, respectively. In Pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only —2.1 D ± 1.4 D. The significant reduction in myopia in Pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm ± 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm ± 0.02 mm and 0.29 mm ± 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in Pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that Pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. Conclusions. Findings demonstrate that chronic administration of the M,-selective muscarinic antagonist, Pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism. Invest Ophthalmol Vis Sci. 1996; 37:1368-1379.
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Pirenzepine prevents form deprivation myopia in a dose dependent manner
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists), 1995Co-Authors: E.m. Leech, Charles L. Cottriall, Neville A. McbrienAbstract:Previous studies have demonstrated that muscarinic antagonists, such as atropine and Pirenzepine, block form deprivation myopia in avian and mammalian models. The aim of the present investigation was to establish dose—response curves for intravitreal and subconjunctivally injected Pirenzepine and to determine receptor specificity. Chicks were monocularly deprived of form vision for five days and received daily injections of either Pirenzepine or saline. Keratometry, retinoscopy and A-scan ultrasonography of axial ocular dimensions were then taken. Intravitreally injected Pirenzepine was effective at preventing form deprivation myopia in a dose dependent manner with an ED50 of 175μg. A 500μg dose totally prevented induced myopia (+0.9 D versus −13.7 D) and axial enlargement (−0.14 mm versus +0.32 mm). Daily subconjunctival injection of Pirenzepine was significantly less effective in preventing form deprivation myopia. Form deprivation myopia could still be induced in animals which had undergone Pirenzepine treatment. Pirenzepine was effective in preventing the axial elongation associated with experimental myopia in a dose dependent manner and via a functional not toxic mechanism.
Charles L. Cottriall - One of the best experts on this subject based on the ideXlab platform.
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The Mx Muscarinic Antagonist Pirenzepine Reduces Myopia and Eye Enlargement in the Tree Shrew
2013Co-Authors: Charles L. Cottriall, Neville A. McbrienAbstract:Purpose. To determine the efficacy of the Mi-selective muscarinic antagonist, Pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Methods. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either Pirenzepine (17.7 fimol; re = 9) or vehicle control (re = 6). Control groups (re = 6) were used to assess the effects of MD, injection regimen, and drug effects. Results. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced —13.2 D ± 0.8 D and —14.1 D ± 0.5 D of axial myopia, respectively. In Pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only —2.1 D ± 1.4 D. The significant reduction in myopia in Pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm ± 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm ± 0.02 mm and 0.29 mm ± 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in Pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia
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prevention of form deprivation myopia with Pirenzepine a study of drug delivery and distribution
Ophthalmic and Physiological Optics, 1999Co-Authors: Charles L. Cottriall, Neville A. Mcbrien, R Annies, E.m. LeechAbstract:Abstract The present study investigated the drug distribution and elimination profiles in ocular tissues of Pirenzepine, a selective M 1 muscarinic antagonist known to inhibit myopia. Results demonstrate that (1) Intravitreal injections of the M 1 selective antagonist Pirenzepine were more effective at preventing form-deprivation myopia than subconjunctival injections. (2) Maximum drug levels were reached within 1 hr for both retina and sclera following intravitreal (28 and 11 nanomole) and subconjunctival (0.25 and 1 nanomole) injection. Intravitreal injection proved a more effective route of drug delivery to all ocular tissues compared to subconjunctival injection. (3) Elimination times of Pirenzepine from ocular tissues were much shorter than those reported for blood plasma. (4) Histological examination revealed no evidence of gross toxic effects at doses effective in inhibiting induced axial myopia. In conclusion, Pirenzepine was effective at reducing form-deprivation myopia in a dose-dependent manner with no evidence of disruption to the retina. However, results were not conclusive as to where Pirenzepine may have its site of action in preventing form-deprivation myopia.
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The M1 muscarinic antagonist Pirenzepine reduces myopia and eye enlargement in the tree shrew.
Investigative ophthalmology & visual science, 1996Co-Authors: Charles L. Cottriall, Neville A. McbrienAbstract:Purpose. To determine the efficacy of the Mi-selective muscarinic antagonist, Pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Methods. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either Pirenzepine (17.7 fimol; re = 9) or vehicle control (re = 6). Control groups (re = 6) were used to assess the effects of MD, injection regimen, and drug effects. Results. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced —13.2 D ± 0.8 D and —14.1 D ± 0.5 D of axial myopia, respectively. In Pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only —2.1 D ± 1.4 D. The significant reduction in myopia in Pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm ± 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm ± 0.02 mm and 0.29 mm ± 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in Pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that Pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. Conclusions. Findings demonstrate that chronic administration of the M,-selective muscarinic antagonist, Pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism. Invest Ophthalmol Vis Sci. 1996; 37:1368-1379.
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Pirenzepine prevents form deprivation myopia in a dose dependent manner
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists), 1995Co-Authors: E.m. Leech, Charles L. Cottriall, Neville A. McbrienAbstract:Previous studies have demonstrated that muscarinic antagonists, such as atropine and Pirenzepine, block form deprivation myopia in avian and mammalian models. The aim of the present investigation was to establish dose—response curves for intravitreal and subconjunctivally injected Pirenzepine and to determine receptor specificity. Chicks were monocularly deprived of form vision for five days and received daily injections of either Pirenzepine or saline. Keratometry, retinoscopy and A-scan ultrasonography of axial ocular dimensions were then taken. Intravitreally injected Pirenzepine was effective at preventing form deprivation myopia in a dose dependent manner with an ED50 of 175μg. A 500μg dose totally prevented induced myopia (+0.9 D versus −13.7 D) and axial enlargement (−0.14 mm versus +0.32 mm). Daily subconjunctival injection of Pirenzepine was significantly less effective in preventing form deprivation myopia. Form deprivation myopia could still be induced in animals which had undergone Pirenzepine treatment. Pirenzepine was effective in preventing the axial elongation associated with experimental myopia in a dose dependent manner and via a functional not toxic mechanism.
Goro Kajiyama - One of the best experts on this subject based on the ideXlab platform.
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Effects of omeprazole and Pirenzepine on enterochromaffin-like cells and parietal cells in rat stomach.
Journal of gastroenterology, 2001Co-Authors: Akira Tari, Yoshitada Kuruhara, Yoshikazu Yonei, Ryo Yamauchi, Shiro Okahara, Koji Sumii, Goro KajiyamaAbstract:The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and Pirenzepine. Methods. The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal Pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. Results. Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas Pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and Pirenzepine were between those produced by treatment with omeprazole alone and Pirenzepine alone. Conclusions. Omeprazole-induced hypergastrinemia and Pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.
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effects of Pirenzepine on omeprazole induced hypergastrinemia and acid suppression in peptic ulcer patients
Journal of Gastroenterology, 1996Co-Authors: Akira Tari, Koji Sumii, Masanori Hamada, Toshiki Kamiyasu, Masaharu Sumii, Youichi Fukino, Ken Haruma, Masaki Inoue, Goro KajiyamaAbstract:Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional Pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and Pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of Pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with Pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and Pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and Pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that Pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional Pirenzepine treatment is also effective in suppressing acid secretion.
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Effects of Pirenzepine on omeprazole-induced gastrin gene expression in rat antral tissues
Digestive diseases and sciences, 1996Co-Authors: Akira Tari, Koji Sumii, Masanori Hamada, Toshiki Kamiyasu, Yoichi Fukino, Masaharu Sumii, Goro KajiyamaAbstract:Pirenzepine has inhibitory effects on gastrin secretion bothin vivo andin vitro. The aim of this study was to determine the mechanism responsible for the suppression of omeprazole-induced hypergastrinemia that occurs with Pirenzepine treatment. The effects were measured in rats treated with oral omeprazole plus intraperitoneal Pirenzepine or saline once daily for seven days in the antrum. The serum gastrin level increased significantly by more than sixfold with omeprazole treatment; additional treatment with Pirenzepine suppressed this increase by 48%. Pirenzepine treatment did not change the level of gastrin mRNA but significantly increased the level of somatostatin mRNA. Combination treatment with omeprazole plus Pirenzepine significantly decreased the gastrin mRNA level to half and significantly increased the somatostatin mRNA level up to 1.4-fold of the levels achieved with omeprazole treatment alone. These results suggest that the stimulatory effect of omeprazole on gastrin synthesis is partially blocked by Pirenzepine via mediation of somatostatin synthesis in the antrum.
Mark Feldman - One of the best experts on this subject based on the ideXlab platform.
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comparison of two antimuscarinic drugs Pirenzepine and propantheline on gastric acid secretion serum gastrin concentration salivary flow and heart rate in patients with duodenal ulcer disease
Alimentary Pharmacology & Therapeutics, 2007Co-Authors: C T Richardson, C C Barnett, John H Walsh, Mark FeldmanAbstract:Effects of orally-administered Pirenzepine and propantheline bromide on food-stimulated gastric acid secretion, serum gastrin concentration, salivary flow and heart rate were compared in 10 duodenal ulcer patients in a placebo-controlled, double-blind study. Pirenzepine inhibited acid secretion by 25, 36 and 44% at doses of 50, 100, and 150 mg, respectively, while propantheline inhibited acid secretion by 32 and 41% at doses of 15 and 45 mg, respectively. None of the doses of Pirenzepine affected food-stimulated serum gastrin concentrations, whereas 45 mg propantheline increased serum gastrin concentration significantly above placebo control. Enhancement of gastrin release by propantheline was not due to its antisecretory effect since intragastric pH after the meal was held constant at 5.0 by intragastric titration in vivo. Pirenzepine had no significant effect on heart rate and little or no inhibitory effect on salivary volume, depending on the dose administered. By contrast, both doses of propantheline increased heart rate and reduced salivary volume significantly (P less than 0.05). Thus, Pirenzepine and propantheline in the doses administered inhibited acid secretion to approximately the same extent but Pirenzepine had fewer effects on other organs.
Akira Tari - One of the best experts on this subject based on the ideXlab platform.
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Effects of omeprazole and Pirenzepine on enterochromaffin-like cells and parietal cells in rat stomach.
Journal of gastroenterology, 2001Co-Authors: Akira Tari, Yoshitada Kuruhara, Yoshikazu Yonei, Ryo Yamauchi, Shiro Okahara, Koji Sumii, Goro KajiyamaAbstract:The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and Pirenzepine. Methods. The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal Pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. Results. Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas Pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and Pirenzepine were between those produced by treatment with omeprazole alone and Pirenzepine alone. Conclusions. Omeprazole-induced hypergastrinemia and Pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.
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effects of Pirenzepine on omeprazole induced hypergastrinemia and acid suppression in peptic ulcer patients
Journal of Gastroenterology, 1996Co-Authors: Akira Tari, Koji Sumii, Masanori Hamada, Toshiki Kamiyasu, Masaharu Sumii, Youichi Fukino, Ken Haruma, Masaki Inoue, Goro KajiyamaAbstract:Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional Pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and Pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of Pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with Pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and Pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and Pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that Pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional Pirenzepine treatment is also effective in suppressing acid secretion.
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Effects of Pirenzepine on omeprazole-induced gastrin gene expression in rat antral tissues
Digestive diseases and sciences, 1996Co-Authors: Akira Tari, Koji Sumii, Masanori Hamada, Toshiki Kamiyasu, Yoichi Fukino, Masaharu Sumii, Goro KajiyamaAbstract:Pirenzepine has inhibitory effects on gastrin secretion bothin vivo andin vitro. The aim of this study was to determine the mechanism responsible for the suppression of omeprazole-induced hypergastrinemia that occurs with Pirenzepine treatment. The effects were measured in rats treated with oral omeprazole plus intraperitoneal Pirenzepine or saline once daily for seven days in the antrum. The serum gastrin level increased significantly by more than sixfold with omeprazole treatment; additional treatment with Pirenzepine suppressed this increase by 48%. Pirenzepine treatment did not change the level of gastrin mRNA but significantly increased the level of somatostatin mRNA. Combination treatment with omeprazole plus Pirenzepine significantly decreased the gastrin mRNA level to half and significantly increased the somatostatin mRNA level up to 1.4-fold of the levels achieved with omeprazole treatment alone. These results suggest that the stimulatory effect of omeprazole on gastrin synthesis is partially blocked by Pirenzepine via mediation of somatostatin synthesis in the antrum.