Except for propranolol, no other Beta-blocker has been studied thoroughly in the prophylaxis of migraine. Of those studied, propranolol, atenolol and timolol were shown to be useful in double-blind clinical trials. The mode, or even the site of action of these drugs in unknown. Possible mechanisms of action are peripheral vascular effects, a central action, 5-HT antagonism, an anxiolytic effect and a multifactorial action. The only common property of the successful drugs is lack of partial agonist activity and their profiles do not fully support any of the above hypotheses. Trials of drugs in the prophylaxis of migraine have in general been unsatisfactory due to the difficulty in controlling many variables. Beta-blockers with differing properties offer an opportunity to define the properties necessary for anti-migraine activity and perhaps shed light on the pathogenesis of migraine.

No abstract

Whole-blood propranolol concentrations were estimated for 12 hours after a single 80 mg oral dose was given in six patients taking cimetidine and two weeks after they had stopped the drug. Mean blood propranolol concentrations were higher throughout the sampling period when the patients were taking cimetidine than when they were not, and the difference was statistically significant between one and four hours (p <0 05). The mean relative bioavailability of propranolol, measured as the area under the concentration time curve, was significantly higher when the patients were taking cimetidine (p < 0 025). The mean increase in bioavailability was 136-5 4 57-6%, and the results were consistent in each subject.It is concluded from these results that cimetidine reduces the hepatic first-pass extraction of propranolol.

This study evaluates the eicosanoid concentration in luteinized unruptured follicles (LUFs) on the ovaries of patients who had been treated with inhibitors of prostaglandin synthetase. Indomethacin, bromfenac, or azapropazone (or a placebo) was administered orally to 41 women during the periovulatory period. Follicular development was monitored by serial ultrasound examinations, and the onset of ovulation was regulated by an injection of hCG. Follicular fluid was aspirated during sterilization by minilaparotomy, which was performed just before the expected time of ovulation. Prostaglandin E2 and PGF2 alpha levels in the fluid were significantly reduced by indomethacin and bromfenac compared to those after placebo treatment. Bromfenac also reduced the follicular fluid leukotriene B4 level. Therefore, the development of luteinized unruptured follicles after treatment with nonsteroidal antiinflammatory drugs appears to be associated with a significant decrease in the synthesis of ovarian eicosanoids.