Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I study of a new fluorinated pyrimidine, 1-hexylcarbamoyl-5-fluorouracil (HCFU), was performed by a multi-institutional clinical study group using a total of 111 patients with histologically proven malignancies. The characteristic toxic effects were a transient hot sensation and pollakiuria, which occurred 15-120 minutes after oral administration of the drug, continued for 30 minutes to 4 hours, and subsided spontaneously. Gastrointestinal disturbances such as nausea, vomiting, diarrhea, and anorexia, which are common with 5-FU administration, also occurred with HCFU but did so less frequently. The maximum tolerated dose for a single oral administration was estimated to be between 12 and 15 mg/kg and the optimal daily dose for continuous administration was considered to be between 9 and 18 mg/kg, with divided daily administration. Fifty-seven patients received 5-19 mg/kg/day of HCFU for > 4 weeks, including 31 patients with > 60 days' treatment. Cumulative doses were from 9.5 to 166.2 g, with a mean of 26.3 g. Hematopoietic toxicity was slight and hepatic toxicity was questionable. No renal or other cumulative toxicity was observed. In ten of the 57 patients, favorable clinical effects were seen: an active decrease in the size of the solid tumor (three patients), the disappearance of ascites (six), and the improvement of intestinal obstruction due to peritoneal carcinomatosis (one).
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PMID:Phase I study of a new antitumor drug, 1-hexylcarbamoyl-5-fluorouracil (HCFU), administered orally: an HCFU clinical study group report. 744 23

A series of novel bicyclic pyrimidine derivatives was prepared as part of a search for NK1 antagonist aimed at the treatment of urinary incontinence. Among them, 3g, a pyrimido[4,5-b][1,5]oxazocine derivative, bearing a 4-acetylpiperazinyl group and a 2-methylphenyl group, was shown to have potent NK1 antagonist activity with a K(B) value of 0.105 nM and markedly increased the effective bladder capacity of guinea pigs (59.4% at 0.3 mg/kg iv and 62.8% at 3 mg/kg id). Furthermore, the effect of 3g on bladder function appeared to differ from that of tolterodine, another classical anti-pollakiuria agent, as determined by the distention-induced rhythmic bladder contraction assay using a urethane-anesthetized guinea pig model. Compound 3g is expected to be a promising agent for the treatment of urinary incontinence.
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PMID:Design, synthesis, and evaluation of novel 2-substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-ones as NK1 antagonists. 1599 86