Trevor R. Norman

Melatonin Rhythm in Human Plasma Saliva

Human plasma saliva were collected at frequent intervals throughout the night after a nocturnal challenge by exposure to 3,000 Ix of light for 1 h in the middle of the night. Melatonin, as measured by radioimmunoassay, was found to correlate highly in plasma saliva, described by a linear regression equation: y = 55x ‐ 2.6 (r = 0.90). The nocturnal melatonin rhythm in saliva was parallel to that observed in plasma. A good correlation was also observed between plasma salivary melatonin on exposure to light. Melatonin in both fluids showed a significant fall during light exposure. Levels returned to normal nocturnal values within 2 h after returning to darkness. These results indicate that salivary melatonin, although lower than plasma melatonin, may be used as an index of pineal glrelease of melatonin. It is suggested that saliva may be useful as a non‐invasive technique for obtaining data on melatonin profiles, especially in pilot‐test screening situations.

The benzodiazepines: a brief review of pharmacology and therapeutics

Benzodiazepines were first discovered in the mid 1950s when Sternbach, a medicinal chemist in New Jersey, began synthesising compounds with a bicyclic nucleus benzo-1, 4-diazepine structure. One compound, chlordiazepoxide (Fig. 1), exhibited sedative, anticonvulsant and muscle relaxant properties, which were confirmed by clinical studies and was launched as an anxiolytic in 1960 under the trade name Librium. A second compound, diazepam (valium), which was more potent and had a broader spectrum of activity than chlordiazepoxide [1], was introduced in 1963. Since then, numerous analogues of the benzodiazepine structure have been developed and introduced into clinical practice.

Relation Between Plasma Antidepressant Concentrations and Clinical Effects

Studies of the plasma levels of antidepressant drugs may improve the treatment of depression and related disorders. It is approximately 20 years since plasma levels of the tricyclic antidepressant drugs first began to be measured. There are close to 100 plasma tricyclic level clinical response studies in the literature today. About one-third find a relation and two-thirds do not. The reasons for this controversy are reviewed and some directions for future research presented.

Antidepressant Drug Measurement: Review of Methods for Clinical Application

Although antidepressants are widely used for the treatment of depressive illness, they are not effective in every patient. In clinical trials as many as 20–30% of patients may fail to respond to adequate doses of drugs administered for an adequate length of time. As an attempt to improve treatment for these nonresponders, Brodie1 suggested that the measurement of plasma concentrations may be of benefit. Given the assumptions it entails, the search for plasma antidepressant-clinical response relations has been vigorously pursued with varying degrees of success. Even the advocates of a “no simple relation” position have defended the value of plasma level monitoring in certain situations.2 A crucial element in the study of these relations is the method of drug analysis. The methods for antidepressants are reviewed.