Memory is a phenomenon of defined neurobiological substrate, enabling undertaking decisions basing on past experience. Owing to its adaptive value it appeared early in the evolution. Memory consists in creating of engrams – the representations of environmental events, and their storage, recall and processing. It is formed in three stages of different nature and duration of the engram: sensory memory (1 s), working memory (approximately 30 s) and durable memory, subdivided into rapidly formed, rather labile short-term memory (up to few hours) and strongly consolidated long-term memory (years and decades). Representations of various type are, depending on their kind, stored either as prone to amnesia explicit declarative memory (subdivided into semantic, episodic and autobiographic), or as implicit, difficult to verbalization, amnesia-resistant procedural memory. The nature of engrams of various types of memory differs. The engrams of long-term memory are stored in changes in the neuronal network, induced by formation of new proteins after activation of expression of various genes resulting from simultaneous stimulation of neurons by glutamate and a monoamine neurotransmitter, leading to phosphorylation and activation of promoters controlling genome. The engrams are localized in the cortex but are sufficiently dispersed to survive the loss of a part on neurons in the network. In the mammalian brain there exist three complementary memory systems, centered on the hippocampus, striatum and amygdala, and involved respectively in spatial and declarative, motor and emotional memory. Studies on animal models have revealed molecular and biochemical aspects of engram formation. On this base the pharmacotherapy of pathological cognitive deficits and methods for enhancement of normal memory may be proposed.
Aim: the aim of this paper was an assessment of the effect of addition of valproate (Depakine-chrono) (sodium valproate + valproic acid) to donepezil treatment on various aspects of mental state and cognitive functions in patients with Alzheimer’s disease.
Methods: forty-one patients with Alzheimer’s disease (24 male, 17 female), aged 50-90 (mean 71+11) years participated in the study. Patients were randomly allocated to two groups: group I – 21 patients, continuing previous treatment with donepezil, and group II – 20 patients receiving donepezil and valproate (Depakine) in dose up to 600 mg/day.
Results: before randomization, initial results of psychometric scales were not different in both groups. After three-month treatment, a significant reduction of depressive symptoms, measured with Cornell Scale for Depression in Dementia, and various behavioral disturbances, measured with Dementia Behavior Disturbance Scale (DBDS) was shown in the group treated with donepezil and valproate. Initial results of neuropsychological tests before randomization were not different in both groups except for the Clock Drawing Test, worse in donepezil and valproate group. Any significant differences between these groups were also not shown after three-month treatment. Patients treated with donepezil plus valproate who had better improvement in DBDS scale obtained also better results on Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Word Fluency Test.
Conclusions: the results of this paper show that the addition of low doses of valproate to donepezil treatment may bring about significant therapeutic benefits.
Escitalopram, the S-enantiomer of citalopram is a novel antidepressant drug. Its predecessor, citalopram, makes a racemate of S (-) and R (+) enantiomers in a 1:1 ratio. Only S-enantiomer of citalopram shows high affinity for serotonin transporter with resulting therapeutic activity, and R-enantiomer is devoid of such properties. Escitalopram produces a unique action on serotonin transporter. Serotonin transporter possesses two binding sites: primary one that mediates the inhibition of serotonin reuptake, and a low affinity allosteric site that modulates a binding of ligand at the primary site. Additional binding of escitalopram to allosteric site stabilizes its binding at the primary site. R-citalopram competing for allosteric site, reduces this effect of escitalopram and thereby attenuates its pharmacological and clinical effects. The clinical trials support these theoretical assumptions. Depressed patients taking escitalopram showed faster and better antidepressant response than patients taking citalopram in comparable doses.
Cytisine is an alkaloid of plant origin known in the health service for over fifty years, having agonistic properties to cholinergic nicotinic receptors. In the recent years, a few interesting results of studies on cytisine that aroused scientists and physicans interest in the drug have been published. The first part of the paper describes the new data, particulary concerning the pharmacodynamics of cytisine, which constitutes a strong indication to the treatment of nicotine addiction and maybe other disorders and diseases. In the further part of the paper the most characteristic results of central and peripheral action of cytisine are discussed. The initial results of clinical studies confirm the efficacy of cytisine comparable with the efficacy of bupropion, the drug used as first-line pharmacotherapy for tobacco dependence. Attention is drawn to cytisine as a paternal substance to the search for other effective therapeutically and safe analogues.
Spinocerebellar ataxias are a group of hereditary neurodegenerative disorders caused by a change in a number of repetitive DNA sequences in a particular gene, i.e. dynamic mutation. These changes cause progressive degeneration of Purkinje cells in cerebellum and neurons of brainstem, which leads to the emergence of typical symptoms: ataxia of gait, posture and limbs, dysarthria, pyramidal and extrapyramidal disorders, amyotrophy, cognitive impairment etc. Currently, treatment of this group of diseases is purely symptomatic. However, research into these disorders resulted in the discovery of molecular pathways and potential therapeutic targets, among others: suppression of neuronal intranuclear inclusions formation, activation of ubiquitin/proteasome pathway, inhibition of caspases and preventing excytotoxicity and oxidative stress. Clinical use of this knowledge may provide the means to developing effective therapeutic strategy of these currently incurable diseases.