We analyzed pharmacological means which are currently in use of Alzheimer’s disease and those which may soon come in use.
Current treatments include the acetylcholine esterase inhibitors (eg, donepezil hydrochloride, galantamine hydrobromide and rivastigmine tartrate), which stabilize the neurotransmitter acetylcholine in the synaptic cleft, and the Nmethyl-D-aspartate receptor antagonist memantine, which counteracts the deleterious effects of high brain concentrations of the excitatory amino acid, glutamate.
Unfortunately current symptomatic treatments of AD are of limited benefi t, as they are not directed at the underlying biological basis of the disease.
Many new drugs are currently in clinical trials. The experiments with drugs targeting Aβ pathology, targeting tau pathology or targeting oxidation and infl ammation will may ultimately lead to tailored treatment strategies.
It is hoped that new drugs will enter the market within the following years to effectively treat patients with Alzheimer’s disease.
Therapeutic drug monitoring (TDM) for lithium is supported on the basis of clearly defi ned therapeutic range. TDM is of particular importance in individuals whose pharmacokinetic behaviour is changing as the result of aging and maturation. The objective of our retrospective study was to evaluate possible association between the lithium concentration and patient age. The study sample was drawn from a data set of 289 patients who had serum lithium estimations between March 2004 and April 2006. 88% of 532 results were maintained at therapeutic range (0.3-1.3 mmol/l) and 10% results were lower than 0.3 mmol/l. There was no difference in the age-dependent distribution of results between females and males. The patients aged 51-60 years had the greatest percentages of results lower than 0.3 mmol/l. Most of the patients (59%) had only single serum lithium estimation. The increased numbers of serum lithium estimations was associated with greater percentages of lithium concentration at therapeutic range (91 vs. 83). The results of our analysis show the signifi - cant part of patients receiving lithium has serum lithium concentration below the therapeutic range. Regular monitoring of lithium serum concentration is likely to improve treatment adherence.
Valproic acid (and its derivatives) is still widely used in the treatment of epilepsy and bipolar disorder. The drug is often administered on a long-term basis in combination with other therapeutics, and that is what generates a risk of pharmacodynamic and pharmacokinetic interactions. The aim of the present paper is to review major pharmacokinetic properties of valproic acid with special emphasis on its interactions with drugs used in internal medicine.
One of the main problems in the therapy of depression is the lack of markers indicating: the acute state of depression, the drug resistance or helpful in foreseeing the therapeutic response. This article is a literature review of current knowledge concerning laboratory markers of depression. Authors discussed the results of clinical trials investigating the immunological and biochemical disturbances (changes in serum level of trace elements, aminoacids and lipids) concomitant with depression. Hormonal tests (e.g. dexamethasone suppression test, fenfl uramine challenge test, TRH stimulation test, assay of serum and CSF level of steroid hormons), platelet and leukocyte markers were also presented.
Polyunsaturated fatty acids omega-3 and omega-6 play an important role in human organism, providing normal functioning of nervous cells, infl uence neurotransmission, make building elements of cellular membranes and take part in the productions of eicasonoids such as prostaglandins, thromboxanes, leukotrienes and lipoxins. Both epidemiological data and the results of neurobiological studies point to an association between a defi ciency of fatty acids of omega-3 type, and depression. The outcome of a number of clinical studies may indicate that the addition of fatty acids to antidepressant treatment augments the effi cacy of the therapy of depression, occurring in the course of the both unipolar and bipolar affective disorders. There are also studies demonstrating therapeutic effect of fatty acids of omega-3 type used as monotherapy, in postpartum depression. The promising results obtained so far on the favorable effects of fatty acids in the treatment of depression need confi rmation in further studies.
A great number of anxiolytics used in the clinical practice is structurally related to 1,4-benzodiazepines. Tofi sopam is the first derivative which differs from the so-called classical benzodiazepines in the position of the nitrogen atoms i.e. in the case of tofi sopam they are vicinals (2,3-).The difference in its structure is suspected to be responsible for the different pharmacological and clinical profile of tofisopam.
Since 60’, several members of the 2,3-benzodiazepine (homophtalazines) family have been synthesized. Some of this compounds- tofizopam (Grandaxin®), girizopam, narizopam – exert anxiolytic and antipsychotic activites. Sites in the brain where actions homophtalazines are mediated differ from those of 1,4-benzodiazepines.
Chemical lesioning of the striato-pallido-nigral system, surgical transactions of the striato-nigral pathway and activation of c-fos expression in basal ganglia after application of 2,3-benzodiazepines suggest that these compounds mainly bind to projecting neurons in the striatum. The mechanism of homophtalazines action is still unknown. Tofizopam increases the affi nity of benzodiazepine receptors (a benzodiazepine binding site on GABA-A receptors) for 1,4-benzodiazepines. The psychoactive effect of tofizopam seems to be mediated by influencing GABAergic transmission, however, in contrast to 1,4-benzodiazepines, tofizopam has no anticonvulsive potency. Tofiopam also exert an inhibitory infl uence on the dopaminergic system. Few studies on the mechanism of action of 2,3-benzodiazepines indicate their possible role in opioid signal transduction. The present paper summarizes the main pharmacological actions of the 2,3-benzodiazepines family.
International Journal of Neuropsychopharmacology (2007), 10, 709–711