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Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.

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To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), a series of heterocycle-condensed purines were designed and synthesized. Some of these new compounds had similar or more potent and selective inhibitory activity

Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs.

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Phosphodiesterase-4 (PDE4), one of eleven PDE enzyme families, specifically catalyzes hydrolysis of cyclic AMP (cAMP); it has four subtypes (PDE4A-D) with at least 25 splice variants. PDE4 plays a critical role in the control of intracellular cAMP concentrations. PDE4 inhibitors produce

Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases.

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cAMP-specific phosphodiesterase inhibitors display a range of activities in vitro and in vivo which suggest they may be useful in the treatment of inflammatory diseases. However, these compounds elicit a number of side-effects which may limit their therapeutic potential. Certain side-effects of PDE4

Inhibition by prostaglandin E 1 of gastric secretion in the dog.

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1. The effect of prostaglandin E(1) (PGE(1)) on gastric secretion was studied in dogs equipped with gastric fundic pouches, either innervated (Pavlov) or denervated (Heidenhain).2. PGE(1) inhibited gastric secretion (volume, acid concentration, acid output, pepsin output) when given either by

Pergolide : A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease.

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CONCLUSIONS The semisynthetic ergotine dopamine agonist pergolide has demonstrated activity at pre- and postsynaptic dopamine D2 receptors in vitro and in vivo animal studies. However, unlike other dopamine agonists such as bromocriptine, pergolide also has agonist activity at dopamine D1 receptors.

Studies on mechanisms of diarrhea induced by fusarenon-X, a trichothecene mycotoxin from Fusarium species: fusarenon-X-induced diarrhea is not mediated by cyclic nucleotides.

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Cardinal signs of red mold toxicosis in man and farm animals are vomiting, nausea, diarrhea, and food refusal. The red mold toxicosis has been suggested to be induced by trichothecenes, which are produced by Fusarium fungi. Fusarenon-X (F-X) is one of the trichothecene mycotoxins. The ip injection

Studies on the production of enterotoxins by Bacillus cereus.

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Evidence is presented for the existence of three distinct enterotoxins detected in concentrated cell-free culture filtrates of selected Bacillus cereus strains. The first was a product capable of stimulating the adenylate cyclase-cyclic-AMP system in intestinal epithelial cells and, possibly through

[Effects of demeclocycline on psychiatric polydipsia in schizophrenic patients].

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Excess intake of water by schizophrenic patients is referred to as psychiatric polydipsia. This symptom causes incontinence, vomiting and hyponatremia, and may sometimes lead to death. We have no effective therapeutic methods other than administrating sodium chloride solution and diuretics, or

Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels.

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Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were

[A case of hypercalcemia with ovarian carcinoma].

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A 45-year-old female manifested lower abdominal fullness and symptoms of hypercalcemia with nausea, vomiting, and thirst. Physical examination showed a right ovarian mass and laboratory data demonstrated hypercalcemia (14.6 mg/dl). The radiographic findings confirmed a right ovarian tumor without

Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

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Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and

Anthrax toxin: pathologic effects on the cardiovascular system.

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Anthrax is a disease caused by infection with spores from the bacteria Bacillus anthracis. After entering the body, the spores germinate into bacteria and secrete a toxin that causes local edema and, in systemic infections, cardiovascular collapse and death. The toxin is a tripartite polypeptide,

Hypercalcemia complicating a megakaryoblastic crisis of chronic myelocytic leukemia.

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A 38-year-old woman with megakaryoblastic chronic myelocytic leukemia (CML) crisis developed recurrent episodes of severe hypercalcemia, manifested by nausea and vomiting and later by dyspnea and hypoxia. The levels of serum parathyroid hormone and serum and urine cyclic AMP were normal. Autopsy

Staphylococcus aureus delta toxin as an enterotoxin.

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The classical enterotoxins are known primarily for their ability to cause emesis and diarrhoea in cases of staphylococcal food poisoning but they also exhibit other biological activities. The seven antigenic types of toxin have molecular weights in the range 25 000-35 000. All types induce emesis in

The potential of PDE4 inhibitors in asthma or COPD.

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At least 11 families of distinct phosphodiesterase (PDE) isoenzymes are known to regulate the function of many cells secondary to altering the intracellular levels of second messengers including cyclic 3'5-monophosphate (cyclic AMP) and cyclic 3'5 guanosine monophosphate (cyclic GMP). While there is

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