Nootropic and smart drug

Aphasia, the loss or impairment of language caused by brain damage, is one of the most devastating cognitive impairments of stroke. Aphasia is present in 21-38% of acute stroke patients and is associated with high short- and long-term morbidity, mortality and expenditure. Recovery from aphasia is possible even in severe cases. While speech-language therapy remains the mainstay treatment of aphasia, the effectiveness of conventional therapies has not been conclusively proved. This has motivated attempts to integrate knowledge from several domains in an effort to plan more rational therapies and to introduce other therapeutic strategies, including the use of intensive language therapy and pharmacological agents.Several placebo-controlled trials suggest that piracetam is effective in recovery from aphasia when started soon after the stroke, but its efficacy vanishes in patients with chronic aphasia. Drugs acting on catecholamine systems (bromocriptine, dexamfetamine) have shown varying degrees of efficacy in case series, open-label studies and placebo-controlled trials. Bromocriptine is useful in acute and chronic aphasias, but its beneficial action appears restricted to nonfluent aphasias with reduced initiation of spontaneous verbal messages. Dexamfetamine improves language function in subacute aphasia and the beneficial effect is maintained in the long term, but its use is restricted to highly selected samples.Pharmacological agents operating on the cholinergic system (e.g. donepezil) have shown promise. Data from single-case studies, case series and an open-label study suggest that donepezil may have beneficial effects on chronic poststroke aphasia. Preliminary evidence suggests that donepezil is well tolerated and its efficacy is maintained in the long term. Randomised controlled trials of donepezil and other cholinergic agents in poststroke aphasia are warranted.

Given the few options that are currently available for patients following ischemic stroke, the search for novel therapeutic approaches becomes more critical. Pharmaceutical intervention strategies for the treatment of stroke include preventative (prophylactic or stroke pretreatment), neuroprotective (early acute post-stroke treatment) and regenerative (delayed post-stroke treatment for long-term benefit) therapeutic approaches. Experimental evidence has suggested that the majority of stroke patients have a slow evolution of brain injury that occurs over several hours. This 'evolving stroke' may ultimately be a realistic target for therapeutic intervention, with the goal of inhibiting the progression of detrimental changes that normally follow the acute ischemic event. Preventing or reducing this delayed cellular injury may improve neurological outcome and also facilitate brain recovery from injury. Significant impact on stroke can be expected as additional research is conducted on biological targets or processes important in facilitating the brain's regenerative capacity following cellular/tissue loss. This review provides updates on stroke prevention therapies (anticoagulant and antiplatelet), the advances in the development of pharmacological agents that target the acute phase of stroke (thrombolytics and neuroprotective drugs), and newly evolving approaches that may facilitate brain regeneration (i.e., neurobehavioral recovery) following brain damage.

BACKGROUND: Stroke is the third leading cause of death in western countries and the leading cause of dependence in activities of daily living. Efforts to reduce its prevalence should therefore be given the highest priority. Uncertainty prevails as to the significance of the various types of intervention. METHODS: This review is based on personal experience, though mostly on a search for relevant literature in the Cochrane Library. RESULTS: Important measures are treatment of hypertension with target area 140/90 mm Hg, anticoagulation in patients with atrial fibrillation and other potential sources of cardioemboli, and for the remainder antiplatelet agents in the form of acetylsalicylic acid, probably preferably combined with dipyradimole. One should also consider drugs reducing serum lipids. INTERPRETATION: Adequate secondary prophylaxis after transient ischaemic attack (TIA) or ischaemic stroke is of potential great benefit in reducing the incidence of new stroke, myocardial infarction or premature vascular death. Standardised guidelines may facilitate implementation of these measures, if they are regularly updated and adjusted to the needs of the individual patient.

Stroke represents the third common cause of death and hospitalization. However, there are yet no drugs that have reliable effects on acute stroke in Japan. Therefore, the development of new drugs that can support patients is required. There are various candidate drugs for acute stroke such as antithrombotic agents, anticoagulants, thrombolytic agents, neuroprotectants, and so on. Recently clinical trials suggest that aspirin may improve outcome, although these studies demonstrated a modest benefit of aspirin. Abciximab (ReoPro) is a human/mouse monoclonal antibody directed against the platelet receptor glycoprotein IIb/IIIa. It appears to be safe and might improve functional outcome. The large randomized trails were started to test the hypothesis that thrombolysis by an intravenous administration of a recombinant tissue type plasminogen activator (rtPA) could restore cerebral blood flow and improve patient outcome in acute ischemic stroke. These results can support the use of intravenous rtPA for stroke treatment within 3 h after onset, but not beyond 3 h. Development of an effective neuroprotective agent for the treatment of acute stroke remains problematic. Antioxidants, MCI-186 and ebselen, have finished phase III of clinical trials in Japan and were effective. We hope that efficacious drugs for acute stroke can be used for patients.

Studies in laboratory animals indicate that the rate and extent of functional recovery after focal brain injury can be modulated by drugs affecting specific central neurotransmitters. Preliminary clinical studies suggest that similar drug effects may occur in humans recovering from stroke. Combined with principles derived from the laboratory, these clinical studies provide important insights to guide the rational design of trials aimed at determining the clinical use of this approach to improving poststroke recovery.

Clin Exp Hypertens 1993;15 Suppl 1:197-210
Middle term evaluation of amlodipine vs nitrendipine: efficacy, safety and metabolic effects in elderly hypertensive patients
Grandinetti O, Feraco E
Department of Cardiology, I.N.R.C.A.-Institute for Geriatric Cardiovascular Diseases, Cosenza, Italy

The aim of the study was to evaluate, in a population of elderly hypertensives, the efficacy for 24 hours, the safety and the effects on carbohydrates and lipids metabolism of amlodipine (A) and nitrendipine (N). After a 3-week placebo wash-out, 50 patients with mild to moderate essential hypertension (HBP) or isolated systolic hypertension (ISH), were randomized in 4 groups treated with once-daily A 5,10mg or N 10,20mg increasing until patients responded to treatment. All subjects were submitted to a 24-hour non invasive ambulatory blood pressure monitoring (ABPM) at the start of the study (t0) and after four weeks of therapy (t4). It was registered a mean daily reduction in the pressure load of 15.0% in group A, 14.1% in group B, 13.9% in group C and 15.6% in group D; (p < 0.001). 82% of the patients treated with A and 85% treated with N resulted "responder". The metabolic parameters considered showed no significant changes. The overall incidence of adverse effects were temporary and extremely limited (2%). As monotherapies, amlodipine and nitrendipine are both suitable for the management of mild to moderate hypertension in elderly.