比较雷尼替丁和西咪替丁对大鼠胃肌条运动的影响
兰州医学院生理教研室 甘肃省兰州市 730000 中国
项目负责人:瞿颂义
Comparative study of ranitidine and cimetidine on contractile activity of isolated gastric muscle strips in rats
Song-Yi Qu, Tian-Zhen Zheng and Wei Li
Department of Physiology, Lanzhou Medical College, Lanzhou 730000, Gansu Province, China.
Song-Yi Qu, Han, Male, July 31, 1944, Shanghai. Graduated at Shanghai Medical University, Master of Medicine, Visiting Scientist of Rochester Medical Center, New York, 1992-1993, Professor and Directior of Department of Physiology, having 25 papers published.
Tel:0086-931-8613596(H)
Supported by Gansu Science Foundation (No.ZR-94-085).
Reported at National Symposium on Gastrointestinal Electric Activity and Motility, Beijing, 1995.
Correspondence to Prof. Song-Yi Qu
Received 29th July 1996
Abstract
AIM To make comparative study of ranitidine and cimetidine, the histamine H2receptor antagonists, on contractile activity of isolated gastric muscle strips in rats.
METHODS Each isolated gastric muscle strip was suspended in a tissue chamber containing 5ml Krebs solution, constantly warmed by water jacked at 37 and supplied with 95% O2 and 5% CO2. The contractile response was measured isometrically on ink￣writing recorders.
RESULTS Ranitidine dose dependently increased the resting tension of fundic and bodied strips and the mean contractile amplitude of antral circular strips. Atropine significantly reduced the excitatory action of ranitidine on the mean contractile amplitude of antral circular strips. Cimetidine decreased the resting tension of fundic and bodies strips and the mean contractile amplitude of antral strips. Indomethacin could not block the inhibitory action of cimetidine.
CONCLUSION The results showed that ranitidine and cimetidine were histamine H2antagonists, which possessed reverse effects on contractile activity of isolated gastric muscle strips of the rats. The excitatory action of ranitidine was mediated via cholinergic receptor partialy, and the inhibitory action of cimetidine was not mediated via endogenous prostaglandin receptor.
Subject headings Stomach/drug effects;Ranitidine ;Cimetidine;Atropine
Qu SY,Zheng TZ, Li W.Comparative study of ranitidine and cimetidine oncontractile activity of isolated gastric muscle strips in rats.XinXiaohuabingxue Zazhi,1997；5(2)：75-76
摘要
目的 比较同是组胺H2受体拮抗剂的雷尼替丁和西咪替丁对大鼠离体胃肌条运动的影响.
方法 把分离的大鼠胃各部位的肌条安置在盛5ml Krebs液的灌流肌槽中，并供给95%O2和5%CO2的气体，外套管内的温水使肌槽保持37恒温.分别加入雷尼替丁和西咪替丁(10-5、10-4和10-3mol/L)等，记录自发等长收缩活动的变化.
结果 雷尼替丁剂量相关地增高胃底、胃体纵行肌和环行肌的张力(10-3mol/L时分别增高264.2±22.3，143.3±20.6，29.2±2.9和10.0±1.5%，P<0.01)，增大胃窦中部和末端环行肌的平均收缩波振幅(10-3mol/L时分别增大65.4±8.8和50.4±8.2%，P<0.01)，阿托品(10-5mol/L)显著减弱雷尼替丁(10-3mol/L)增大胃窦中部和末端环行肌的平均收缩波振幅(分别为15.6±4.7和25.2±4.3%，P<0.01).西咪替丁降低胃底、胃体纵行肌和环行肌的张力(10-3mol/L时分别为-40.0±5.2，-21.5±1.8, -21.1±3.3和-7.5±1.0%,P<0.01)，减小胃窦纵行肌、中部和末端环行肌的平均收缩波振幅(10-3mol/L时分别为-78.6±11.4, -93.8±6.3和-92.9±7.2%, P<0.01)，消炎痛(10-5mol/L)未阻断西咪替丁(10-3mol/L)的抑制作用(P>0.05).
结论 虽然雷尼替丁和西咪替丁都是组胺H2受体拮抗剂，但对大鼠离体胃肌条运动的影响是相反的；雷尼替丁的兴奋作用部分经由胆碱能受体介导，西咪替丁的抑制作用未经由内源性前列腺素受体的途径.
主题词 雷尼替丁;西咪替丁;阿托品;胃/药物作用
瞿颂义，郑天珍，李伟.比较雷尼替丁和西咪替丁对大鼠胃肌条运动的影响.新消化病学杂志, 1997；5(2)：75-76
INTRODUCTION
As for specific and potent blockade of histamine H2receptors, ranitidine and cimetidine can both reduce gastric acid secretion during the physiological events and inhibit gastric acid secretion elicited by histamine or pentagastrin. Ranitidine is more potent than cimetidine in the effective therapy of duodenal ulcer and reflux oesophagitis by diminishing gastro-oesophageal acid reflux with fewer untoward effects[1-2]. Besides, some histamine H2-receptor antagonists can affect gastointestinal motility and possess gastroprokinetic activity[3]. In this paper, we compared the effects of ranitidine and cimetidine, the H2-receptor antagonists with different chemical structures on isolated gastric muscle strips in rats and investigated the mechanism involved.
MATERIALS AND METHODS
Wistar rats, weighing 200-250g, were sacrificed with the whole stomach removed. Muscle strips (8mm×2mm) were cut, parallel to either the circular or the longitudinal fibers and named circular muscle (CM) and longitudinal muscle (LM) of fundus, CM and LM of the body, distal and middle CM and LM of antrum and CM of pylorus[4]. Each strip with the mucosa removed was suspended in a tissue chamber containing 5ml Krebs solution, constantly warmed by circulating water jacked at 37 and supplied with 95% O2 and 5% CO2. One end of the strip was fixed to a hook on the bottom of the chamber while the other end was connected by a thread to an external isometric force transducer (JZ-BK, BK) at the top. Motility of gastric strips in 8 tissue chambers were simultaneously recorded on ink-writing recorders (LMS-ZB, Cheng-Du)[5]. Preparations were subjected to 1g load tension and washed with 5ml Krebs solution every 20 minutes. After one-hour equilibration, ranitidine (10-5, 10-4, 10-3mol/L) or cimetidine (10-5, 10-4, 10-3mol/L) or stropine (10-3mol/L) or indomethacin (10-5mol/L) given 3 minutes before administration of cimetidine (10-3mol/L) was added in the tissue chamber separately. 50μl drugs were added in a 5ml bath so that the final molar concentration was achieved.We measured the resting tension of fundic and bodied strips, the mean contractile amplitude of antral strips and the motility index (MI=∑[amplitude×duration]) of pyloric circular strip. Frequency of contractions was determined by counting the contraction waves. The results were presented as percentage (%) increases of the control spontaneous contraction (x-±s) The data were statistically analyzed by Student′s t test, and P values <0.05 were considered as significant.
RESULTS
Effect of ranitidine on the spontaneous contraction of gastric stripsRanitidine dose dependently increased the resting tension of LM and CM o f fundus and body and the mean contractile amplitude of distal and middle CM of antrum, whereas it did not affect the mean contractile amplitude of antral LM an d the motility index of pyloric CM (Figure 1, Table 1). The frequency of contrac tions of gastric strips at each site did not change significantly (P>0.05) .
Figure 1 Effects of ranitidine and cimetidine on the resting tension of the fundus and body, and the mean contractile amplitude of antrum in rats. L(C)M, longitudial (circular) muscle; A1(A2) distal (middle) CM of antrum; aP<0.05, bP0.01 vs control; x-±s(%) increase.
Table 1 Effect of ranitidine on the restine tension of the fundus and body, and the mean contractile amplitude of antrum in rats
L(C)M, longitudinal (circular) muscle; aP<0.05, bP<0.01 vs control; 0, no effect; x-±s(%) increase.
Table 2 Effect of cimetidine on the resting tension of the fundus and body, and the mean controactile amplitude of antrum in rats
L(C)M, longitudinal (circular) muscle; aP<0.05, bP<0.01 vs control; 0, no effect; x-±s(%) increase.
Atropine (10-5mol/L) given 3 minutes before administration of ranitidine (10-3mol/L) did not affect the ranitidine action on the resting tension of LM and CM of fundus and body, but significantly reduced the increasing action of ranitidine on the mean contractile amplitude of middle and distal CM of antrum (15.6%±4.7% vs 65.4%±8.8%, P<0.01; 25.2%±4.3% vs 50.4%±8.2%, P<0.01, respectively).
Effect of cimetidine on the spontaneous contraction of gastric stripsCimetidine decreased the resting tension of the LM and CM of the fundus and body and the mean contractile amplitude of LM and distal and middle CM of antrum, whereas it did not affect the motility index of pyloric CM (Figure, Table 2). Cimetidine (10-3mol/L) slowed the frequency of LM and CM of the body (4.4±0.2 vs 3.6±0.2, P<0.01; 4.1±0.1 vs 3.5±0.2cmp/min, P<0.01, respectively). As cimetidine (10-3mol/L) usually abolished the contraction waves of antrum, it was difficult to count the antral frequency.Indomethacin (10-5mol/L) given 3 minutes before administration of cimetidine (10-3mol/L) did not affect the decreasing action of cimetidine on the gastric strips of rats.
DISCUSSION
In vivo experiments, ranitidine stimulated gastrointestinal motility during the postprandial period and increased gastric emptying[2-3,6]. In vitro stu dies, ranitidine increased the contractile amplitude of antral CM in guinea pig[7] and the contraction of fundic strips in rabbits[8]. In the present study, we observed that ranitidine dose dependently increased the resting tension of fundic and bodied strips and the mean contractile amplitude of antral CM. Atropine significantly reduced the increasing action of ranitidine on the mean contractile amplitude of antral CM which agreed with previous reports that ranitidine increased gastric emptying and motility by inhibition of acetylcholinesterase and/or enhancement of acetylcholine release[1,3].It was reported that cimetidine might inhibit gastric emptying and was weaker than ranitidine in affecting gastrointestinal motility[6]. Prostaglandins regulated gastrointestinal motility and inhibited contractile motility of distal stomach[9]. As indomethacin (a prostaglandin synthesis inhibitor) could not block the decreasing action of cimetidine on the gastric strips of rats, it suggested that cimetidine inhibited action was not mediated via endogenous prostaglandin receptor. Cimetidine slowed the frequency of strip contraction, leading to the decrease of contractile activity. Although ranitidine and cimetidine are the histamine H2receptor antagonists inhibiting gastric acid secretion, but the chemical structure of ranitidine (a furan ring) is different from that of cimetidine (imidazolic compound). Obviously, the excitatory or inhibitory effects of the drugs on gastrointestinal motility were not related to their actions at H2receptor sites, which suggested that we should consider the effect on gastrointestinal motility when we treat the peptic ulcer using H2-receptor antagonists. Some histamine H2-receptor antagonists might be selected as gastroprokinetic agents. More recently, nizatidine (a new histamine H2-receptor antagonist) was found to have similar potency to ranitidine in stimulating gastrointestinal motility[10].
REFERENCES1 Gwee MCE, Cheah LS. Actions of cimetidine and ranitidine at some cholinergicsites: implications
in toxicology and anesthesia. Life Sci,1986;39(5):383-388
2 Scarpignato C, Tramacere R, Zappia L. Antisecretory and anti ulcer effectof the H2-receptor antagonist
famotidine in the rat: comparison withranitidine. Br J Pharmacol, 1987;92(1):153-159
3 Ueki S, Seiki M, Yoneta T, Aita H, Chaki K, Hori Y, et al. Gastroprokineticactivity of nizatidine,a new H2-receptor antagonist, and its possiblemechanism of action in dogs and rats.
J Pharmacol Exp Ther,1993;264(1):152-157
4 Qu SY, Song CW, Lee KY, Chey WY. Action of secretin and/or cholecystokininon gastric smooth
muscle in rats. Gastroenterology,1993;104(2-4):A567
5 Qu SY, Zheng TZ, Li W. Effect of cholecystokinin and secretin on contractileactivity of isolated
gastric muscle strips in guinea pigs. Acta PhysiologicaSinica, 1995;47(3):305-309 (in Chinese)
6 Bertaccini G, Scarpignato C. Histamine H2 antagonists modify gastricemptying in the rat.
Br J Pharmcol, 1982;77(3):443-448
7 Parkman HP, Pagano AP, Ryan JP. Ranitidine and nizatidine stimulate antralsmooth muscle
contractility via an excitatory cholinergic mechanism.Gastroenterology, 1994;106(2.4):A553
8 Kounenis G, Koutsoviti PM, Elezoglou A, Voutsas A. Comparative study of the H2-receptor
antagonists cimetidine, ranitidine, famotidine and nizatidine on the rabbit stomach fundus and
sigmoid colon. J Pharmacobiodyn,1992;15(10):561-565
9 Sanders KM. Role of prostaglandins in regulating gastric motility. Am J Physiol, 1984;247(1):G117-G126
10 Ohira Y, Hanyu N, Aoki T, Hashimoto Y, Tikura M, Fukuda S. Effects of various histamine
H2-receptor antagonists on gastrointestinal motility and gastric emptying.
J Smooth Muscle Res, 1993;29(4):131-142, 百拇医药
项目负责人:瞿颂义
Comparative study of ranitidine and cimetidine on contractile activity of isolated gastric muscle strips in rats
Song-Yi Qu, Tian-Zhen Zheng and Wei Li
Department of Physiology, Lanzhou Medical College, Lanzhou 730000, Gansu Province, China.
Song-Yi Qu, Han, Male, July 31, 1944, Shanghai. Graduated at Shanghai Medical University, Master of Medicine, Visiting Scientist of Rochester Medical Center, New York, 1992-1993, Professor and Directior of Department of Physiology, having 25 papers published.
Tel:0086-931-8613596(H)
Supported by Gansu Science Foundation (No.ZR-94-085).
Reported at National Symposium on Gastrointestinal Electric Activity and Motility, Beijing, 1995.
Correspondence to Prof. Song-Yi Qu
Received 29th July 1996
Abstract
AIM To make comparative study of ranitidine and cimetidine, the histamine H2receptor antagonists, on contractile activity of isolated gastric muscle strips in rats.
METHODS Each isolated gastric muscle strip was suspended in a tissue chamber containing 5ml Krebs solution, constantly warmed by water jacked at 37 and supplied with 95% O2 and 5% CO2. The contractile response was measured isometrically on ink￣writing recorders.
RESULTS Ranitidine dose dependently increased the resting tension of fundic and bodied strips and the mean contractile amplitude of antral circular strips. Atropine significantly reduced the excitatory action of ranitidine on the mean contractile amplitude of antral circular strips. Cimetidine decreased the resting tension of fundic and bodies strips and the mean contractile amplitude of antral strips. Indomethacin could not block the inhibitory action of cimetidine.
CONCLUSION The results showed that ranitidine and cimetidine were histamine H2antagonists, which possessed reverse effects on contractile activity of isolated gastric muscle strips of the rats. The excitatory action of ranitidine was mediated via cholinergic receptor partialy, and the inhibitory action of cimetidine was not mediated via endogenous prostaglandin receptor.
Subject headings Stomach/drug effects;Ranitidine ;Cimetidine;Atropine
Qu SY,Zheng TZ, Li W.Comparative study of ranitidine and cimetidine oncontractile activity of isolated gastric muscle strips in rats.XinXiaohuabingxue Zazhi,1997；5(2)：75-76
摘要
目的 比较同是组胺H2受体拮抗剂的雷尼替丁和西咪替丁对大鼠离体胃肌条运动的影响.
方法 把分离的大鼠胃各部位的肌条安置在盛5ml Krebs液的灌流肌槽中，并供给95%O2和5%CO2的气体，外套管内的温水使肌槽保持37恒温.分别加入雷尼替丁和西咪替丁(10-5、10-4和10-3mol/L)等，记录自发等长收缩活动的变化.
结果 雷尼替丁剂量相关地增高胃底、胃体纵行肌和环行肌的张力(10-3mol/L时分别增高264.2±22.3，143.3±20.6，29.2±2.9和10.0±1.5%，P<0.01)，增大胃窦中部和末端环行肌的平均收缩波振幅(10-3mol/L时分别增大65.4±8.8和50.4±8.2%，P<0.01)，阿托品(10-5mol/L)显著减弱雷尼替丁(10-3mol/L)增大胃窦中部和末端环行肌的平均收缩波振幅(分别为15.6±4.7和25.2±4.3%，P<0.01).西咪替丁降低胃底、胃体纵行肌和环行肌的张力(10-3mol/L时分别为-40.0±5.2，-21.5±1.8, -21.1±3.3和-7.5±1.0%,P<0.01)，减小胃窦纵行肌、中部和末端环行肌的平均收缩波振幅(10-3mol/L时分别为-78.6±11.4, -93.8±6.3和-92.9±7.2%, P<0.01)，消炎痛(10-5mol/L)未阻断西咪替丁(10-3mol/L)的抑制作用(P>0.05).
结论 虽然雷尼替丁和西咪替丁都是组胺H2受体拮抗剂，但对大鼠离体胃肌条运动的影响是相反的；雷尼替丁的兴奋作用部分经由胆碱能受体介导，西咪替丁的抑制作用未经由内源性前列腺素受体的途径.
主题词 雷尼替丁;西咪替丁;阿托品;胃/药物作用
瞿颂义，郑天珍，李伟.比较雷尼替丁和西咪替丁对大鼠胃肌条运动的影响.新消化病学杂志, 1997；5(2)：75-76
INTRODUCTION
As for specific and potent blockade of histamine H2receptors, ranitidine and cimetidine can both reduce gastric acid secretion during the physiological events and inhibit gastric acid secretion elicited by histamine or pentagastrin. Ranitidine is more potent than cimetidine in the effective therapy of duodenal ulcer and reflux oesophagitis by diminishing gastro-oesophageal acid reflux with fewer untoward effects[1-2]. Besides, some histamine H2-receptor antagonists can affect gastointestinal motility and possess gastroprokinetic activity[3]. In this paper, we compared the effects of ranitidine and cimetidine, the H2-receptor antagonists with different chemical structures on isolated gastric muscle strips in rats and investigated the mechanism involved.
MATERIALS AND METHODS
Wistar rats, weighing 200-250g, were sacrificed with the whole stomach removed. Muscle strips (8mm×2mm) were cut, parallel to either the circular or the longitudinal fibers and named circular muscle (CM) and longitudinal muscle (LM) of fundus, CM and LM of the body, distal and middle CM and LM of antrum and CM of pylorus[4]. Each strip with the mucosa removed was suspended in a tissue chamber containing 5ml Krebs solution, constantly warmed by circulating water jacked at 37 and supplied with 95% O2 and 5% CO2. One end of the strip was fixed to a hook on the bottom of the chamber while the other end was connected by a thread to an external isometric force transducer (JZ-BK, BK) at the top. Motility of gastric strips in 8 tissue chambers were simultaneously recorded on ink-writing recorders (LMS-ZB, Cheng-Du)[5]. Preparations were subjected to 1g load tension and washed with 5ml Krebs solution every 20 minutes. After one-hour equilibration, ranitidine (10-5, 10-4, 10-3mol/L) or cimetidine (10-5, 10-4, 10-3mol/L) or stropine (10-3mol/L) or indomethacin (10-5mol/L) given 3 minutes before administration of cimetidine (10-3mol/L) was added in the tissue chamber separately. 50μl drugs were added in a 5ml bath so that the final molar concentration was achieved.We measured the resting tension of fundic and bodied strips, the mean contractile amplitude of antral strips and the motility index (MI=∑[amplitude×duration]) of pyloric circular strip. Frequency of contractions was determined by counting the contraction waves. The results were presented as percentage (%) increases of the control spontaneous contraction (x-±s) The data were statistically analyzed by Student′s t test, and P values <0.05 were considered as significant.
RESULTS
Effect of ranitidine on the spontaneous contraction of gastric stripsRanitidine dose dependently increased the resting tension of LM and CM o f fundus and body and the mean contractile amplitude of distal and middle CM of antrum, whereas it did not affect the mean contractile amplitude of antral LM an d the motility index of pyloric CM (Figure 1, Table 1). The frequency of contrac tions of gastric strips at each site did not change significantly (P>0.05) .
Figure 1 Effects of ranitidine and cimetidine on the resting tension of the fundus and body, and the mean contractile amplitude of antrum in rats. L(C)M, longitudial (circular) muscle; A1(A2) distal (middle) CM of antrum; aP<0.05, bP0.01 vs control; x-±s(%) increase.
Table 1 Effect of ranitidine on the restine tension of the fundus and body, and the mean contractile amplitude of antrum in rats
| Ranitidine | 10-5mol/L | 10-4mol/L | 10-3mol/L | |
| Fundus | LM | 12.1±4.8a(n=12) | 74.6±13.5b(n=13) | 264.2±22.3b(n=12) |
| CM | 1.3±0.9(n=12 | 25.8±3.0b(n=13) | 143.3±20.0b(n=12) | |
| Body | LM | 0.8±0.8(n=12) | 13.8±2.2b(n=12) | 29.2±2.9b(n=13) |
| CM | 0(n=12) | 2.5±1.3(n=12) | 10.0±1.5b(n=14) | |
| Antrum | LM | 0(n=12) | 0(n=13) | 2.5±1.7(n=14) |
| Middle CM | 2.5±1.8(n=12) | 20.3±7.3a(n=15) | 65.4±8.8b(n=16) | |
| Distal CM | 1.7±1.3(n=12) | 4.1±1.5a(n=14) | 50.4±8.2b(n=12) |
L(C)M, longitudinal (circular) muscle; aP<0.05, bP<0.01 vs control; 0, no effect; x-±s(%) increase.
Table 2 Effect of cimetidine on the resting tension of the fundus and body, and the mean controactile amplitude of antrum in rats
| Ranitidine | 10-5mol/L | 10-4mol/L | 10-3mol/L | |
| Fundus | LM | -1.7±1.1(n=12) | -10.4±2.8b(n=12) | -40.0±5.2b(n=12) |
| CM | 0(n=12) | -4.6±1.4a(n=12) | -21.5±1.8b(n=13) | |
| Body | LM | 0(n=12) | -1.5±1.0(n=13) | -21.1±3.3b(n=14) |
| CM | 0(n=12) | 0(n=14) | -7.5±1.0b(n=14) | |
| Antrum | LM | 0(n=13) | 0(n=13) | -78.6±11.4b(n=14) |
| Middle CM | 4.0±2.9(n=15) | 09±0.9(n=12) | -93.8±6.3b(n=16) | |
| Distal CM | -1.7±0.9(n=12) | -2.9±1.8(n=12) | -92.9±7.2b(n=14) |
L(C)M, longitudinal (circular) muscle; aP<0.05, bP<0.01 vs control; 0, no effect; x-±s(%) increase.
Atropine (10-5mol/L) given 3 minutes before administration of ranitidine (10-3mol/L) did not affect the ranitidine action on the resting tension of LM and CM of fundus and body, but significantly reduced the increasing action of ranitidine on the mean contractile amplitude of middle and distal CM of antrum (15.6%±4.7% vs 65.4%±8.8%, P<0.01; 25.2%±4.3% vs 50.4%±8.2%, P<0.01, respectively).
Effect of cimetidine on the spontaneous contraction of gastric stripsCimetidine decreased the resting tension of the LM and CM of the fundus and body and the mean contractile amplitude of LM and distal and middle CM of antrum, whereas it did not affect the motility index of pyloric CM (Figure, Table 2). Cimetidine (10-3mol/L) slowed the frequency of LM and CM of the body (4.4±0.2 vs 3.6±0.2, P<0.01; 4.1±0.1 vs 3.5±0.2cmp/min, P<0.01, respectively). As cimetidine (10-3mol/L) usually abolished the contraction waves of antrum, it was difficult to count the antral frequency.Indomethacin (10-5mol/L) given 3 minutes before administration of cimetidine (10-3mol/L) did not affect the decreasing action of cimetidine on the gastric strips of rats.
DISCUSSION
In vivo experiments, ranitidine stimulated gastrointestinal motility during the postprandial period and increased gastric emptying[2-3,6]. In vitro stu dies, ranitidine increased the contractile amplitude of antral CM in guinea pig[7] and the contraction of fundic strips in rabbits[8]. In the present study, we observed that ranitidine dose dependently increased the resting tension of fundic and bodied strips and the mean contractile amplitude of antral CM. Atropine significantly reduced the increasing action of ranitidine on the mean contractile amplitude of antral CM which agreed with previous reports that ranitidine increased gastric emptying and motility by inhibition of acetylcholinesterase and/or enhancement of acetylcholine release[1,3].It was reported that cimetidine might inhibit gastric emptying and was weaker than ranitidine in affecting gastrointestinal motility[6]. Prostaglandins regulated gastrointestinal motility and inhibited contractile motility of distal stomach[9]. As indomethacin (a prostaglandin synthesis inhibitor) could not block the decreasing action of cimetidine on the gastric strips of rats, it suggested that cimetidine inhibited action was not mediated via endogenous prostaglandin receptor. Cimetidine slowed the frequency of strip contraction, leading to the decrease of contractile activity. Although ranitidine and cimetidine are the histamine H2receptor antagonists inhibiting gastric acid secretion, but the chemical structure of ranitidine (a furan ring) is different from that of cimetidine (imidazolic compound). Obviously, the excitatory or inhibitory effects of the drugs on gastrointestinal motility were not related to their actions at H2receptor sites, which suggested that we should consider the effect on gastrointestinal motility when we treat the peptic ulcer using H2-receptor antagonists. Some histamine H2-receptor antagonists might be selected as gastroprokinetic agents. More recently, nizatidine (a new histamine H2-receptor antagonist) was found to have similar potency to ranitidine in stimulating gastrointestinal motility[10].
REFERENCES1 Gwee MCE, Cheah LS. Actions of cimetidine and ranitidine at some cholinergicsites: implications
in toxicology and anesthesia. Life Sci,1986;39(5):383-388
2 Scarpignato C, Tramacere R, Zappia L. Antisecretory and anti ulcer effectof the H2-receptor antagonist
famotidine in the rat: comparison withranitidine. Br J Pharmacol, 1987;92(1):153-159
3 Ueki S, Seiki M, Yoneta T, Aita H, Chaki K, Hori Y, et al. Gastroprokineticactivity of nizatidine,a new H2-receptor antagonist, and its possiblemechanism of action in dogs and rats.
J Pharmacol Exp Ther,1993;264(1):152-157
4 Qu SY, Song CW, Lee KY, Chey WY. Action of secretin and/or cholecystokininon gastric smooth
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