Clinical implications of the pharmacology of serotonin reuptake inhibitors.

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action.

Betaxolol and glucose-insulin relationships: studies in normal subjects taking glibenclamide or metformin.

1. The potential interaction between selective beta 1-adrenoceptor blockers and sulphonylureas or biguanides was studied by comparing the beta 1-adrenoceptor antagonist betaxolol with placebo in 12 normal subjects taking glibenclamide or metformin in a single-blind crossover group study. 2.

A double-blind placebo-controlled study of the efficacy and tolerability of ebastine against hayfever in general practice patients.

Ebastine is an H1 antihistamine. Using a double-blind, parallel group randomized study design, the efficacy and the tolerability of oral ebastine (10 mg daily escalating to 40 mg daily according to clinical need) was compared over 4 weeks during 1986 with matching placebo in 40 general practice patients suffering from hayfever. Ebastine (19 patients) was more effective (P less than 0.

Research and development of new medicines.

In order that a new chemical entity may be marketed as a drug its pharmacological effects must first be evaluated using animals. Its bioavailability must also be determined and toxicological studies are performed to assess its acute and chronic toxicity, mutagenicity, effects on fertility, perinatal effects, teratogenicity and carcinogenicity. If the results of efficacy and toxicity studies in animals are favourable, the drug is then tested in a few human volunteers, followed by pilot studies and large-scale clinical trials.

A multicentre open comparison of isosorbide-5-mononitrate and nifedipine given prophylactically to general practice patients with chronic stable angina pectoris.

A total of 126 patients from general practice with chronic stable angina pectoris entered the treatment phase of this open, randomized, crossover comparison of 20 mg isosorbide-5-mononitrate, and 20 mg nifedipine. Both treatments were given orally, three times daily, for 4 weeks and sublingual administration of glyceryl trinitrate was allowed throughout. Over the whole treatment period, there was no statistically significant difference between treatments for anginal attacks.

Chlortenoxicam pharmacokinetics in young and elderly human volunteers.

The pharmacokinetics of chlortenoxicam, a new non-steroidal anti-inflammatory drug, have been compared in young and elderly healthy human volunteers. Chlortenoxicam was found to have a relatively short mean elimination half-life of about 4 hours, with considerable inter-subject variability, but there was no significant difference between young and elderly subjects. There was no evidence of accumulation with repeated administration.

Recent developments in the use of nitrates for treatment of angina pectoris.

Organic nitrates are effective in the treatment and prophylaxis of angina pectoris. The major clinical problem of tolerance may be avoided if the daily plasma concentrations of the active metabolite, isosorbide-5-mononitrate are maintained at 100-300 ng/ml. The most promising development in achieving this is the use of sustained release preparations.

Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia.

Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam.