Drugs online research references
groton.pfizer.com
Intramolecular endo-cyclization reactions of N-acyliminium ions have seen wide application for the synthesis of heterocyclic compounds. The corresponding exocyclic variant, which would provide 1-aminotetralin derivatives, for example, has little precedent. We have discovered that acyclic N-acylcarbamates can be readily reduced to the corresponding N-acylhemiaminal derivatives in high yield using DIBAL as the reducing agent. These intermediates are remarkably stable and, if desired, can be purified and stored. The acyclic N-acylhemiaminals undergo both intra- and intermolecular nucleophilic addition reactions mediated by strong Lewis acids, such as TiCl(4). Diastereoselectivity, induced either by a substituent on the newly formed ring, or by utilizing a chiral ester on the carbamic acid, was disappointingly low. This methodology was successfully applied to the synthesis of the racemic form of the marketed antidepressant sertraline.
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cyf-kr.edu.pl
1. Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its different regions), in the present study we examined the uptake of psychotropic drugs by vertically cut slices of whole brain, grey (cerebral cortex) and white (corpus callosum, internal capsule) matter of the brain and by neuronal and astroglial cell cultures. 2. Moreover, we assessed the contribution of lysosomal trapping to total drug uptake (total uptake=lysosomal trapping+phospholipid binding) by tissue slices or cells conducting experiments in the presence and absence of 'lysosomal inhibitors', i.e., the lysosomotropic compound ammonium chloride (20 mM) or the Na(+)/H(+)-ionophore monensin (10 microM), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5 microM. 3. Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline, fluoxetine, sertraline) and neuroleptics (promazine, perazine, thioridazine) were higher in the grey matter and neurones than in the white matter and astrocytes, respectively. Lysosomal trapping of the psychotropics occurred mainly in neurones where thioridazine sertraline and perazine showed the highest degree of lysosomotropism. 4. Distribution interactions between antidepressants and neuroleptics took place in neurones via mutual inhibition of lysosomal trapping of drugs. 5. A differential number of neuronal and glial cells in the brain may mask the lysosomal trapping and the distribution interactions of less potent lysosomotropic drugs in vertically cut brain slices. 6. A reduction (via a distribution interaction) in the concentration of psychotropics in lysosomes (depot), which leads to an increase in their level in membranes and tissue fluids, may intensify the pharmacological action of the combined drugs.
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J Clin Psychiatry. 2001;62 Suppl 24:18-22.
Diagnosing and treating depression in the elderly.
Nelson JC.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06504, USA.
As the population of people over 65 years of age increases, clinicians will see more cases of late-life depression. Currently, the rates of depression in the elderly are higher for nursing home patients and other medical inpatients and outpatients than for the noninstitutionalized, non-medically ill elderly. Depression in the elderly may be difficult to diagnose because of factors such as late onset, comorbid medical illness, dementia, and bereavement, but depression is not a natural part of aging. People who are depressed have increased suffering, impaired functioning, and increased mortality. Fortunately, antidepressants have been shown to effectively treat late-life depression. While monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are efficacious for treating depression in the elderly, their side effect profiles may be difficult and even dangerous for some older patients. However, serotonin selective reuptake inhibitors (SSRIs) and other second generation antidepressants appear to be both effective and better tolerated in the elderly. Since elderly patients may be more sensitive to drugs, clinicians may need to closely monitor these patients for dosing, side effects, and drug-drug interactions.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11676429&dopt=Abstract
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