Multi Target Neuroprotective and Neurorestorative Anti-Parkinson and Anti-Alzheimer Drugs Ladostigil and M30 Derived From Rasagiline.

Multi target neuroprotective and neurorestorative anti-Parkinson and anti-Alzheimer drugs ladostigil and m30 derived from rasagiline.

Exp Neurobiol. 2013 Mar; 22(1): 1-10
Youdim MB

Present anti-PD and -AD drugs have limited symptomatic activity and devoid of neuroprotective and neurorestorative property that is needed for disease modifying action. The complex pathology of PD and AD led us to develop several multi-target neuroprotective and neurorestorative drugs with several CNS targets with the ability for possible disease modifying activity. Employing the pharmacophore of our anti-parkinson drug rasagiline (Azilect, N-propagrgyl-1-R-aminoindan), we have developed a series of novel multi-functional neuroprotective drugs (A) [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase and brain selective monoamine-oxidase (MAO) A/B inhibitory activities and (B) the iron chelator-radical scavenging-brain selective monoamine oxidase (MAO) A/B inhibitor and M30 possessing the neuroprotective and neurorescuing propargyl moiety of rasagiline, as potential treatment of AD, DLB and PD with dementia. Another series of multi-target drugs (M30, HLA-20 series) which are brain permeable iron chelators and potent selective brain MAO inhibitors were also developed. These series of drugs have the ability of regulating and processing amyloid precursor protein (APP) since APP and alpha-synuclein are metaloproteins (iron-regulated proteins), with an iron responsive element 5″UTR mRNA similar to transferring and ferritin. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats after oral doses. After chronic but not acute treatment, it inhibits MAO-A and -B in the brain. Ladostigil acts like an anti-depressant in the forced swim test in rats, indicating a potential for anti-depressant activity. Ladostigil prevents the destruction of nigrostriatal neurons induced by infusion of neurotoxin MPTP in mice. The propargylamine moiety of ladostigil confers neuroprotective activity against cytotoxicity induced by ischemia and peroxynitrite in cultured neuronal cells. The multi-target iron chelator M30 has all the properties of ladostigil and similar neuroprotective activity to ladostigil, but is not a ChE inhibitor. M30 has a neurorestorative activity in post-lesion of nigrostriatal dopamine neurons in MPTP, lacatcystin and 6-hydroxydopamine animal models of PD. The neurorestorative activity is related to the ability of the drug to activate hypoxia inducing factor (HIF) which induces the production of such neurotrophins as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and erythropoietin as well as glia-derived neurotrophic factor (GDNF). The unique multiple actions of ladostigil and M30 make the potentially useful drugs for the treatment of dementia with Parkinsonian-like symptoms and depression. HubMed – depression


Living with chronic low back pain: a metasynthesis of qualitative research.

Chronic Illn. 2013 Apr 12;
Snelgrove S, Liossi C

OBJECTIVES: The purpose of this qualitative metasynthesis is to articulate the knowledge gained from a review of qualitative studies of patients’ experiences of chronic low back pain. METHODS: Meta-ethnographic methodology guided the review of 33 articles representing 28 studies published in English in peer-reviewed journals between 2000 and 2012. A systematic comparison of the main themes from each study was conducted and ‘synthesised’ to create superordinate themes. RESULTS: Three overarching interrelated themes were identified: the impact of chronic low back pain on self; relationships with significant others that incorporated two streams – health professionals and the organisation of care and relationships with family and friends; coping with chronic low back pain. Coping strategies were predominantly physical therapies, medication and avoidance behaviours with very few successful strategies reported. Professional and family support, self-efficacy, motivation, work conditions and exercise opportunities influenced pain experiences. Review authors’ recommendations included psychological therapies, education, the facilitation of self-management strategies and support groups. DISCUSSION: The review substantiates chronic low back pain as complex, dynamic and multidimensional, underpinned by experiences of persistent distressing pain, loss, and lowered self-worth, stigma, depression, premature aging, fear of the future. Future research should address the paucity of longitudinal studies, loss and issues of ethnicity, gender, ageing. HubMed – depression


Illness beliefs and psychological outcome in people with Parkinson’s disease.

Chronic Illn. 2013 Apr 12;
Simpson J, Lekwuwa G, Crawford T

Illness beliefs are important predictors of psychological outcome in people with chronic illness and evidence suggests these could also be significant in furthering our understanding of psychological functioning in people with Parkinson’s disease. Illness beliefs are specific, dynamic representations of an illness and cover dimensions such as cause, identity, consequences and controllability. Eighty-one people with Parkinson’s disease completed a series of questionnaires to provide demographic, clinical and psychosocial data, which were then used to assess the relative impact of illness beliefs on their psychological functioning. Psychological functioning was assessed by measuring levels of depression, anxiety, stress, positive affect and emotional well-being. Hierarchical block regression indicated that illness beliefs were important independent predictors across some but not all outcomes and the results emphasised the importance of testing new predictors against more established predictors of outcome such as physical functioning and self-esteem. The illness beliefs most important in psychological outcome in people with PD were causal beliefs (particularly in psychosocial causes) and illness coherence (the level of understanding of the illness). The therapeutic potential of psychosocial variables was discussed given that these can be modified during therapy and this change can positively influence psychological outcome. HubMed – depression


Estimer la prevalence de la depression a partir des DME.

Can Fam Physician. 2013 Apr; 59(4): e212-3
Puyat JH, Marhin WW, Etches D, Wilson R, Martin RE, Sajjan KK, Wong ST

HubMed – depression



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