Harada M, Mayuzumi K, Yano S
J Pharmacobiodyn. 1981 May;4(5):309-16. doi: 10.1248/bpb1978.4.309.
In rats exposed to restraint and water immersion stress, inhibitory effects of atropine (ATR) and chlorpromazine (CPZ) on stress-induced gastric ulceration and motility were studied to clarify which of central and peripheral origins was responsible for these effects. The drug dose ratio of peripheral (intravenous, i.v.) route versus central (intracerebroventricular, i.c.v.) route required to produce an approx. 50% inhibition of gastric ulceration or motility was estimated. Gastric ulceration was prevented by pretreatment with each drug via either route, and there was no great difference in the dose ratio of each drug (i.v.:i.c.v. = 4:1) for the inhibition. The stress-enhanced gastric motility was immediately depressed by each drug via either route. This inhibitory effect of CPZ was short-lasting as compared with that of ATR, and the complete blockade was observed after administration of i.v. ATR or i.c.v. CPZ at higher doses. The ATR dose ratio for this inhibition was less than 10, while the CPZ dose ratio was from 10 to 25. The treatment with CPZ, but not with ATR, caused a definite change in EEG patterns, along with a decrease in body temperature or heart rate. The effect of pretreatment with ATR or CPZ on gastric motility during stress was also investigated. Only the administration of ATR, via either route, appreciably inhibited the gastric motility. Thus, it was suggested that: (1) the inhibitory effect of ATR on gastric motility may be of peripheral rather than central origin, while that of CPZ predominantly of central origin; (2) the anti-ulcerogenic effect of ATR and CPZ may be predominantly of peripheral origin, and the mechanisms involved in ATR may be associated with inhibition of gastric motility, which is different from those in CPZ.
在遭受束缚和水浸应激的大鼠中，研究了阿托品（ATR）和氯丙嗪（CPZ）对应激诱导的胃溃疡和胃动力的抑制作用，以阐明这些作用是由中枢还是外周起源引起的。估算了通过外周（静脉内，i.v.）途径与中枢（脑室内，i.c.v.）途径产生约50%胃溃疡或胃动力抑制所需的药物剂量比。通过任何一种途径预先使用每种药物均可预防胃溃疡，并且每种药物的抑制剂量比（i.v.:i.c.v. = 4:1）没有很大差异。每种药物通过任何一种途径均可立即抑制应激增强的胃动力。与ATR相比，CPZ的这种抑制作用持续时间较短，在静脉注射ATR或脑室内注射较高剂量的CPZ后观察到完全阻断。这种抑制作用的ATR剂量比小于10，而CPZ剂量比为10至25。CPZ治疗而非ATR治疗导致脑电图模式发生明确变化，同时体温或心率降低。还研究了预先使用ATR或CPZ对应激期间胃动力的影响。只有通过任何一种途径给予ATR才能明显抑制胃动力。因此，提示：（1）ATR对胃动力的抑制作用可能起源于外周而非中枢，而CPZ的抑制作用主要起源于中枢；（2）ATR和CPZ的抗溃疡作用可能主要起源于外周，且ATR涉及的机制可能与胃动力抑制有关，这与CPZ不同。
