The effect of cholinergic 'blockade' on human memory performance as a model for the effect of cholinergic depletion in clinical disorders was investigated. A wide range of memory functions was assessed in 70 subjects, using tests which were identical or closely similar to those which have previously been employed in clinical studies of Alzheimer and Korsakoff patients. In addition, a physiological measure of the degree of central cholinergic blockade was included, as well as measures of subjective arousal and objective attention. It was found that cholinergic blockade had no significant effect on the more passive aspects of primary (or 'working') memory, namely span tests and a measure of verbal short-term forgetting; in this, it contrasts with the marked deficits seen in Alzheimer-type dementia. On the other hand, cholinergic blockade produced impairment at a visuospatial short-term forgetting test, and at a verbal test in which the distractor task was made more difficult. On tests of secondary memory, cholinergic blockade produced a pattern similar to that seen in the anterograde amnesia of Alzheimer and Korsakoff patients, namely a pronounced impairment in learning verbal and visuospatial material, a 'normal' forgetting rate once learning had been accomplished, and relative preservation of the response to priming and of skill learning (procedural memory). Cholinergic blockade, however, did not produce a retrograde amnesia, nor did it affect the recall of temporal context or of long-established semantic knowledge. This pattern of results is compared with that obtained in previous studies of Alzheimer and Korsakoff patients.

Melatonin and cortisol values in plasma were measured hourly over 24 hours in six depressed patients and six normal volunteers before treatment and after one and three weeks of treatment with desipramine. The normal volunteers were further tested one week after withdrawal of desipramine. The mydriatic effects of tyramine and phenylephrine eye drops were also recorded in the normal volunteers. In neither group of subjects did desipramine treatment reduce melatonin secretion, suggesting that functionally significant down-regulation of beta andrenoceptors was not caused by this treatment. Melatonin secretion was significantly increased after three weeks of treatment in depressed patients. This increase was not found in normal subjects.

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients wh...

The growth hormone responses to clonidine (1.3 micrograms/kgm) and apomorphine (0.005 mg/kgm) have been measured in 8 drug free patients with endogenous depression. In these patients the growth hormone responses to clonidine were significantly smaller than to apomorphine. As these doses of clonidine and apomorphine have previously been reported to cause similar growth hormone responses in normal subjects, these findings support the hypothesis of a defect in the adrenergic but not the dopaminergic regulation of growth hormone in patients with endogenous depression.

The growth hormone response to clonidine was measured in ten drug-free recovered patients, seven of whom had previously been tested when endogenously depressed, and compared with the response in ten individually matched controls. In eight of the patients there was an impairment of the growth hormone response, despite clinical recovery, although the hypotensive effect of clonidine in these patients was normal. This is suggestive of a persisting abnormal alpha2-adrenoceptor function in forebrain regions after recovery from an episode of endogenous depression, and may represent a trait marker for this condition.