Search

In this double-blind, randomized study the efficacy of the ergoloid compounds, co-dergocrine mesylate and nicergoline, in the rehabilitation of patients with ischaemic stroke was investigated. A group of 30 patients was treated daily with 60 mg nicergoline, orally, and a second group of 27 patients was given 1.8 – 6 mg co-dergocrine mesylate, orally or intramuscularly, daily (depending on the time since the initial ischaemic insult) for 6 months. Outcome measures included: motoricity index (limb function); Sandoz Clinical Assessment Geriatric (SCAG) scale; psychometric tests to assess functions such as attention, psychomotor performance, perception and sensory and short-term memory; conventional and computerized electroencephalography; and P300 and reaction time measures. The results showed improvements in some aspects such as limb function ( P < 0.05), SCAG score ( P < 0.01) and some electrophysiological parameters ( P < 0.01) after treatment with both drugs. Though statistically significant most of the changes were not large. The efficacy of both drugs was qualitatively similar. The quantitative difference in some aspects in favour of nicergoline could be attributed to differences in the mechanisms of action of the two drugs, although it is also possible that the difference may reflect the dosages used. Nootropic drugs may induce a condition that facilitates the effects of cognitive training.

OBJECTIVE:To provide information about research evaluating antioxidants in Alzheimer disease (AD) and to discuss the potential role of β-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD therapy.DATA SOURCES:Studies, review articles, and editorials identified from MEDLINE searches (from 1989 to 1997) and bibliographies of identified articles.STUDY SELECTION:Studies and review articles addressing antioxidant, antihypertensive, and ergoloid derivative pharmacotherapy research.DATA EXTRACTION:Pertinent information was selected and the data synthesized into a review format.DATA SYNTHESIS:AD is a progressive neuropsychiatric disorder of unknown etiology. Studies evaluating the possible association between a free radical mechanism in AD and the potential role of antioxidants are reviewed. Additionally, the role of β-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD management are discussed.CONCLUSIONS:Preliminary evidence suggests that antioxidants may have a protective effect against the development of AD. Additional prospective, double-blind, placebo-controlled studies are needed to determine the role of antioxidants in the prevention and management of AD. Understanding the role of antioxidants in AD may suggest alternative agents that have similar pharmacologic activity. β-Blockers may be an option to control agitation in AD patients for whom anxiolytics or antipsychotics are ineffective or are contraindicated because of their adverse effect profiles. Other agents that may have a role in AD therapy include angiotensin-converting enzyme inhibitors, nimodipine, and ergoloid derivatives. Clonidine and guanfacine have thus far shown little promise in improving cognitive function in AD. Further prospective, double-blind, placebo-controlled trials will be necessary to elucidate the role of these agents in AD management.

The ergot alkaloids possess strong pharmacological effects and are important drugs with widespread clinical uses. The ergot alkaloid preparations manufactured by Gedeon Richter Chemical Works Ltd have a very low active substance content (e.g. 1.0 mg in each Secadol (0.4 g) coated tablet); therefore a sensitive method of determination must be used. Because of this constraint the differential pulse voltammetric behaviour of ergot alkaloids was studied in respect of the effects of pH and composition of media and an automated FIA system with amperometric detection has been used to develop a selective and sensitive method for the routine quantitative assay of these alkaloids. A short summary is given of the experimental evidence to substantiate the stoichiometric equation proposed for the electrochemical oxidation of the lysergic acid type of ergot alkaloids, the mechanism may be generally applicable for compounds having the ergoloid skeleton. In the course of the work it was concluded that a simple DC amperometric method of detection in a FIA system could be applied to determine the content of ergot alkaloids of different pharmaceutical preparations. A suitable method designed to meet current analytical requirements has been developed and validated.

The pharmacokinetics and bioavailability of ergoloid mesylates following single administrations of various dose levels (3-9 mg), dosage forms (oral swallow and sublingual tablets, solution) and under different dosing conditions (fasted, with meal) were studied in young healthy volunteers. Male and female subjects showed a similar rate and extent of bioavailable ergoloid after drug treatment. The absorption of ergoloid using either the tablet dosage forms or the drug administered as a solution was rapid, with peak levels of about 60-80 pg ml-1 mg-1 dose achieved after 0.6 to 1.3 h. The elimination half-life for ergoloid in plasma was 2-5 h. Administration of drug with food had no effect on the extent of absorption (AUC) but lowered the absorption rate. This resulted in a reduction of (by 25 per cent) and delay in (by 1 h) achieving peak levels (Cmax). Increasing the ergoloid dose caused a proportional increase in the AUC, but a smaller than proportional increase for Cmax. The tablet formulations provided similar AUCs as the solution; the objective of the sublingual tablet formulation to provide improved bioavailability over the swallow tablet via circumvention of first-pass metabolism was therefore not realized. Transient decreases in blood pressure after ergoloid treatment paralleled the plasma level profiles. Higher ergoloid levels were paired with the larger pressure decreases.