Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first use of ICI 169,369, a selective S2 receptor antagonist, in acute and prophylactic treatment of migraine. Ten selected patients documented their migraine attacks over a 2-month period of open treatment with ICI 169,369, 30 mg orally, for acute therapy. They compared this treatment with others they had experience of. Four of these patients undertook a pharmacokinetic study comparing drug absorption in an acute attack to that when symptom-free. Prophylaxis was then commenced with the same drug, 30 mg bd. Patients recorded symptoms in diary cards noting the effects of treatment on the usual frequency and severity of their attacks. The pharmacokinetic study showed that drug absorption could be markedly impaired during an acute attack. Nevertheless, in 35 attacks treated acutely, half the patients reported some efficacy apparent to them. One third of patients considered ICI 169,369 to be better treatment on this one occasion than their own usual medication. Some benefit was also noted during prophylaxis. There was a statistically significant reduction in attack frequency from the baseline observed during acute therapy only, but this was arguably compatible with placebo response. S2 receptor antagonism may have some beneficial effect in acute or prophylactic treatment of migraine, but it is not marked and does not support S2 receptor activation being important in its pathogenesis.
Headache 1990 May
PMID:Serotonin S2 receptors and migraine: a study with the selective antagonist ICI 169,369. 237 Jan 33

Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
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PMID:FDA drug approval summaries: fulvestrant. 1249 Jul 35