Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-(2,2-Diphenylethyl)adenosine (DPEA) has been identified as a potential antipsychotic agent acting via stimulation of adenosine receptors. The projected human therapeutic dose, based on animal studies, is 2-3 mg/kg. DPEA has been tested for potential toxicity in mice, rats, dogs and monkeys. Following single oral doses, median lethal dose values were approximately 10-fold greater in rats than in mice, although similar clinical signs including reduced activity, prostration, and necrosis of the tail were seen in both species. DPEA was well tolerated at daily doses up to 40 mg/kg in rats for 2 weeks. A no observed effect level (NOEL) was not identified in the dog or monkey studies. Reduced activity, dacryorrhea, ptosis, hypothermia, necrosis of the tail, and death occurred in rats given 120 and 160 mg/kg. Pathologic changes consisted of pancreatitis, gastric erosion/ulceration, lymphocyte depletion of the thymus, and pulmonary congestion and hemorrhage at 80 mg/kg or greater. In dogs, sporadic emesis was noted at 12.5 mg/kg and greater, and significant pathologic changes consisted of coronary arteritis associated with myocardial lesions and lymphocyte depletion at 25 and 50 mg/kg, pancreatic acinar necrosis at 50 mg/kg, and renal tubular degeneration at 12.5 mg/kg and greater. Emesis and depression were noted at 25 and 50 mg/kg in monkeys. Renal tubular dilatation and degeneration at 25 and 50 mg/kg were noted in the monkeys. These studies demonstrated that DPEA produced a range of adverse effects in common laboratory animal species.
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PMID:Preclinical toxicity studies of an adenosine agonist, N-(2,2-diphenylethyl) adenosine. 187 77

Cyclopiazonic acid (CPA) was found to have many pharmacological properties in common with the antipsychotic drugs chlorpromazine and reserpine. Thus, in mice CPA at ip doses of 5-14 mg/kg body weight produced hypokinesia, hypothermia, catalepsy, ptosis, sedation without loss of righting reflex, tremor, gait disturbance, dyspnoea, opisthotonus, atypical convulsion and prolonged barbiturate-induced sleep. The ip LD50 of CPA was found to be 13 +/- 0.05 mg/kg. The tremors induced by near-lethal doses of CPA were associated with voluntary or forced movements (action tremors); they worsened during the days following treatment, but they were weak compared with the exhausting and continuous tremors of the whole body caused by 20 mg tremorine/kg (used for comparison). When death occurred only 24-259 min after administration of CPA (11-14 mg/kg), it was preceded by dypsnoea, cyanosis, opisthotonus and clonic leg movements and tonic extension of hind legs (convulsions). When death was delayed (2-6 days after CPA administration), it was preceded by prostration, ptosis, hypothermia, tremor and cessation of food and water intake resulting in cachexia; convulsions were not seen in this group of mice. CPA did not affect the rate of convulsion or death caused by either maximal electroshock or metrazol administration but it did delay the onset of metrazol-induced seizures. In rabbits, 10 mg CPA/kg body weight initially produced tachycardia, tachypnoea and sedation with an activated electroencephalogram. Of three rabbits given 10 mg CPA/kg one died, and in this rabbit slow delta waves were seen just before and during a brief period with clonic leg movements. In this animal death was accompanied by tonic extension of the hind legs, respiratory arrest and cardiac fibrillation; and epileptiform EEG was not seen at any time. The unexpected EEG activation with sedation in rabbits treated with CPA was similar to the effect of reserpine on EEG.
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PMID:Toxicity and neuropharmacology of cyclopiazonic acid. 404 83

Audiogenic seizures associated with loss of weight, prostration, piloerection, palpebral ptosis and motor deficiency were induced after sound stimulation of determined frequency and amplitude in magnesium-deficient DBA/2 mice. These symptoms were maintained when standard diet conditions (1700 ppm Mg2+) were restored. In contrast, mice were protected from audiogenic seizure in a dose related manner when Crassostrea gigas extract (JCOE) were added to the diet for 10 consecutive days. Although a rational explanation for this protective effect has not yet been determined, it is assumed that it might be due to a chelating complex formed between Mg2+ and taurine, which enhance the uptake of Mg2+.
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PMID:Protective effect of Crassostrea gigas extract on audiogenic seizures in magnesium deficient mice. 975 10