New Synthetic Agent for the Induction of Ovulation: Preliminary Trials in Women

Abstract

DiscussionMedazepam, a benzodiazepine, is being used in Europe increasingly for the symptomatic relief of neurotic anxiety, but there have been relatively few carefully controlled trials comparing it with established anti-anxiety drugs. The results of our initial investigation on inpatients confirm that it is effective in relieving anxiety. The optimum dose was 10 mg three times a day, and since there were no abnormalities in liver function or blood tests in this group the drug was considered to be safe for outpatient use.The results of a double-blind crossover comparison show that medazepam 10 mg three times a day is superior to amylobarbitone 60 mg three times a day for the relief of anxiety in outpatients (P<0-01). This was shown by the patients' responses to one or other of the drugs used in an attempt to relieve their presenting symptoms. This comparison might be criticized on the ground that the dose of amylobarbitone was too low. Higher doses are certainly more effective in relieving anxiety, but at the expense of increased drowsiness. Our own previous experience with amylcvbarbitone suggests that a 60 mg dose three times a day is probably the best dose for most outpatients. In addition to its overall superiority, medazepam was particularly useful for the relief of ruminations (P<0-05) and phobias (P<0-01). Drowsiness and ataxia were not major problems with medazepam, but we should add that this series contained no elderly patients, who seem to be most vulnerable to those side effects.A comparison of the results of this trial with a trial of chlordiazepoxide 20 mg three times a day and amylobarbitone 60mg three times a day (Jenner, Kerry, and Parkin, 1961) suggests that medazepam 10mg three times a day is at least as therapeutically effective as chlordiazepoxide 20 mg three times a day. In the present study 24 out of 29 patients (83 %) preferred medazepam, whereas the previous trial showed chlordiazepoxide to be preferred by 59 out of 77 patients (77%).A previous comparison of diazepam 5 mg three times a day and amylobarbitone 50 mg three times a day (Jenner and Kerry, 1967) showed that 15 out of 19 patients (7904) preferred diazepam for the relief of their anxiety. This suggests that 10 mg of medazepam three times a day also has about the same activity as 5 mg of diazepam three times a day.To evaluate a new tranquillizer is always difficult, and one would now like to see the results obtained by comparing medazepam with other established tranquillizers. The use of these drugs is often accompanied by initial enthusiasm, to be followed later by disappointment. Psychiatrists are often forced to use the available tranquillizers for the relief of anxiety when perhaps psychotherapy would be more appropriate. This was an outpatient trial and no attempt could be made to keep environmental factors uniform; indeed, it would not have been desirable to do so, since the purpose was to assess the drugs as used in daily practice. It seems that medazepam 10 mg three times a day might offer symptomic relief of anxiety to ...

New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

“…The drug was found to be an extremely potent postcoital contraceptive in the rat [4,5]. Unfortunately, ICI 46,474 did not exhibit antifertility properties in women, in fact, quite the opposite, it induced ovulation [6,7]. As a result, the medicine was, at one time, marketed in the United Kingdom for the induction of ovulation in subfertile women with a functional hypothalamo-pituitary-ovarian axis.…”

Induction of ovulation with an estrogen antagonist, tamoxifen.

“…Regarding the time interval between the commencement of treatment and ovulation, Klopper and Hall (1971) reported the period of 6 to 20 days after the oral administration (10 days on average), and Macourt (1974) did a lag of 6 to 20 days (11 days on average). Our results were similar to those reported by Williamson and Ellis (1973) and Tajima et al (1977) and the time lag was between day 13 and 46 of the treatment, i.e.…”

“…Since ovulation-inducing effect of tamoxifen was firstly proved by Klopper and Hall (1971) (1977,1978,1979). An ovulatory induction rate of 73.3% in the present study is consistent with the results reported by those investigators, which ranged between 61.2 and 81.3% with an exception of 95% repored by Ruiz-Velasco et al (1979).…”

Tamoxifen: Catalyst for the change to targeted therapy

“…Walpole advanced clinical testing of ICI 46,474 in both "the control of hormone dependent tumours" and "the regulation of the sexual cycle." Clinical testing was initiated to evaluate activity to treat breast cancer at the Christie Hospital in Manchester and the Princess Margaret Hospital, Birmingham (13,14) and reproductive cycle studies proceeded elsewhere (15). In 1972, all conclusions were reviewed by ICI Ltd Pharmaceuticals Division in Alderley Park, Macclesfield, Cheshire.…”

“…Unlike the results observed in the rat, ICI 46,474 (16) was not a contraceptive in humans. The drug induced ovulation and could potentially be used as a profertility agent (15). ICI 46,474 exhibited modest activity as a breast cancer therapy which was equivalent to historical controls treated with high dose oestrogens or androgens (13).…”