From cysteamine to MPTP: structure-activity studies with duodenal ulcerogens

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Toxicol. Pathol.; (United States)

DOI:https://doi.org/10.1177/019262338801600213· OSTI ID:6596761

Szabo, S; Cho, C H

Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting from an etiologic and pathogenetic point of view is the dopaminergic neurotoxin MPTP, which shows structural similarities with toluene. The chemically-induced duodenal ulcers are similar and localized on the anterior and posterior wall of the duodenal bulb. Both cysteamine and MPTP affect endogenous dopamine; MPTP is especially potent in depleting central dopamine and inducing lesions in the substantia nigra. MPTP given in high doses induces Parkinson's disease-like syndrome and gastric ulcers. Cysteamine and propionitrile also cause dyskinesia in large and multiple doses. The motility disorders and duodenal ulcers are abolished by dopamine agonists. Cysteamine and MPTP have been known to increase and decrease gastric acid secretion, respectively. However, both compounds induced duodenal dysmotility, decreased bicarbonate production, and reduced its delivery from distal to proximal duodenum. These factors decrease acid neutralization in the duodenal bulb and contribute to duodenal ulceration. Thus, studies with animal models may reveal endogenous mediators and specific receptors which might be involved in the pathogenesis of duodenal ulceration. Specific structure-activity studies in toxicology may lead to new insights in the pathogenesis and pharmacology of a poorly understood human disorder such as duodenal ulceration. 39 references.

• Research Organization: Brigham and Women's Hospital, Boston, MA (USA)
• OSTI ID: 6596761
• Journal Information: Toxicol. Pathol.; (United States), Journal Name: Toxicol. Pathol.; (United States) Vol. 16:2; ISSN TOPAD
• Country of Publication: United States
• Language: English

Related Subjects

550900 -- Pathology
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATED AROMATICS
AMINES
ANTIGENS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BIOLOGICAL MODELS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CYSTAMINE
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
DOCUMENT TYPES
DOPAMINE
DRUGS
GASTROINTESTINAL TRACT
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
INTESTINES
MATERIALS
NEUROREGULATORS
NITRILES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PATHOGENESIS
PATHOLOGICAL CHANGES
PHENOLS
POLYPHENOLS
PROPIOLONITRILE
PYRIDINES
RADIOPROTECTIVE SUBSTANCES
REVIEWS
SMALL INTESTINE
STRUCTURE-ACTIVITY RELATIONSHIPS
SYMPATHOMIMETICS
TOLUENE
TOXIC MATERIALS
TOXICITY
TOXINS
ULCERS