PMID- 381206 OWN - NLM STAT- MEDLINE DCOM- 19791024 LR - 20210526 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 24 IP - 3 DP - 1979 Jun TI - Chlorpromazine reverses diarrhea in piglets caused by enterotoxigenic Escherichia coli. PG - 900-5 AB - The effect of chlorpromazine (CPZ) on diarrhea caused by enterotoxigenic Escherichia coli was tested in piglets since CPZ has been shown to be a potent antagonist to enterotoxins in vitro in a cell system and in vivo in a mouse model. Experimental diarrhea was induced in three litters of newborn piglets which were infected by mouth with 2 x 10(9)E. coli bacteria, which produce heat-labile (LT) and heat-stable (ST) enterotoxins. Treatment with CPZ given intramuscularly 1 h after the onset of diarrhea reversed fluid secretion in small intestine as well as dehydration, as judged by clinical criteria. A dose of 5 mg of CPZ per kg of body weight completely normalized the intestinal-fluid content measured 4 h after diarrhea developed, whereas 1 to 2 mg of CPZ per kg of body weight was somewhat less effective but still caused significant reduction of fluid (P < 0.001). Studies with radioactive [(35)S]CPZ showed preferential and dose-dependent uptake of (35)S in the intestinal mucosa, the radioactivity being evenly distributed in the membranes of both crypt and villus cells. The enzyme adenylate cyclase, which probably mediates the cellular effects of LT, was shown to have two- to threefold higher activity in the infected than in the uninfected animals. This activation was reduced about 50% by the CPZ treatment (2 mg/kg of body weight). In a preliminary field trial the effect of CPZ was tested in a spontaneous outbreak of diarrhea in piglets due to enterotoxinogenic E. coli. The animals were treated either with oral electrolyte solution and standard antimicrobial agents only (controls) or with 1 mg of CPZ per kg of body weight intramuscularly in addition to this treatment. The mean duration of diarrhea in CPZ-treated animals was significantly shorter, 4.1 h (n = 23), than that in controls, 7.2 h (P < 0.05). FAU - Lonnroth, I AU - Lonnroth I FAU - Andren, B AU - Andren B FAU - Lange, S AU - Lange S FAU - Martinsson, K AU - Martinsson K FAU - Holmgren, J AU - Holmgren J LA - eng PT - Journal Article PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Enterotoxins) RN - EC 4.6.1.1 (Adenylyl Cyclases) RN - U42B7VYA4P (Chlorpromazine) SB - IM MH - Adenylyl Cyclases/metabolism MH - Animals MH - Chlorpromazine/*therapeutic use MH - Diarrhea/*drug therapy/physiopathology/veterinary MH - Enterotoxins/biosynthesis MH - Escherichia coli Infections/*drug therapy/physiopathology/veterinary MH - Intestinal Mucosa/metabolism MH - Swine MH - Swine Diseases/drug therapy PMC - PMC414392 EDAT- 1979/06/01 00:00 MHDA- 1979/06/01 00:01 PMCR- 1979/06/01 CRDT- 1979/06/01 00:00 PHST- 1979/06/01 00:00 [pubmed] PHST- 1979/06/01 00:01 [medline] PHST- 1979/06/01 00:00 [entrez] PHST- 1979/06/01 00:00 [pmc-release] AID - 10.1128/iai.24.3.900-905.1979 [doi] PST - ppublish SO - Infect Immun. 1979 Jun;24(3):900-5. doi: 10.1128/iai.24.3.900-905.1979.