Twenty benzamide derivatives with and without EPS side effects have been compared in terms of their physicochemical properties and 3-D molecular modeling using the HyperChem program and the CQSAR program. While no single determining physicochemical property can be identified with the EPS side effects. Similarities and differences of the 3-D structures do exist among the ones with and without EPS side effects. These 3-D models of the ones without EPS side effects may be used tor further development of each subclass of therapeutic agents with improved pharmacological profile.
Carisoprodol at 100 mg/Kg dosage level was found to increase the pentobarbital induced sleeping time in mice significantly, while phenylbutazone at 14 mg/Kg did not cause a significant change. The sex difference of the pentobarbital sleeping time was found to be dose dependent. The female mice were found to be more sensitive to the dose increase than the male. Carisoprodol at 50 mg/Kg level did not reduce the motor activity significantly. Antazoline phosphate at 14 mg/Kg reduced the motor activity by 34 percent. When these two drugs were given together the motility was reduced by more than 50 percent (P<0.005).
As ageing progresses the levels of sex hormones decrease in the human body. In the male population, the decrease or absence of testosterone leads to decreased strength and stamina, thin bones and a low sex drive (1). In the female population, the immediate symptoms of menopause include irregular periods, painful sexual intercourse due to vaginal dryness, hot flushes and night sweats (2). Lack of oestrogen also leads to the risk of developing osteoporosis and cardiovascular diseases. In this report, the authors will mainly discuss the effects of hormone therapy (HT) in menopausal women. Available current clinical data on the effects of calcium supplementation with and without HT, exercise, exercise plus calcium and exercise with HT on bone loss are presented. The effects of transdermal and oral oestrogen therapy (OT) on serum lipids are discussed. Commercially-available HT products, their indications, dosages, contra-indications, side-effects and drug interactions are compared. Alternative therapies for menopausal symptoms with Chinese traditional herbs, and a comparison of the molecular structures of phytoestrogens with estradiol and diethylstilbestrol are examined (3, 4). A list of medicinal herbs and foods reported to elicit an oestrogenic response in animals is compiled.
From the deductive point of view, neurotransmitter receptors can be divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic (alpha- and beta-), dopaminergic, serotoninergic (5-HT1 approximately 5-HT5), and histaminergic (H1 and H2). Selective agonists and antagonists of each receptor subtype can have specific useful therapeutic applications. For understanding the molecular mechanisms of action, an inductive method of analysis is useful.The aim of the present study is to examine the structure-activity relationships of agents acting on G-protein coupled receptors.Representative sets of G-PCR agonists and antagonists were identified from the literature and Medline [P.M. Walsh (2003) Physicians' Desk Reference; M.J. O'Neil (2001) The Merck Index]. The molecular weight (MW), calculated logarithm of octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole moment (DM), E(lumo) (the energy of the lowest unoccupied molecular orbital, a measure of the electron affinity of a molecule and its reactivity as an electrophile), E(homo) (the energy of the highest occupied molecular orbital, related to the ionization potential of a molecule, and its reactivity as a nucleophile), and the total number of hydrogen bonds (H(b)) (donors and receptors), were chosen as molecular descriptors for SAR analyses.The data suggest that not only do neurotransmitters share common structural features but their receptors belong to the same ensemble of G-protein coupled receptor with seven to eight transmembrane domains with their resultant dipoles in an antiparallel configuration. Moreover, the analysis indicates that the receptor exists in a dynamic equilibrium between the closed state and the open state. The energy needed to open the closed state is provided by the hydrolysis of GTP. A composite 3-D parameter frame setting of all the neurotransmitter agonists and antagonists are presented using MW, Hb and mu as independent variables.It appears that all neurotransmitters examined in this study operate by a similar mechanism with the G-protein coupled receptors.
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Among the three major causes of death in developed countries, namely, cardiovascular diseases including heart attack, stroke, and all forms of cancer, the first two are associated with hypertension. Because of the important health impact, many antihypertensive agents have been introduced in the last 50 years. In this review, we shall focus our attention on the following groups: (1) renin inhibitors, (2) calcium channel blockers, (3) α- and β-adrenergic blockers, and (4) angiotensin converting enzyme (ACE) inhibitors.
A literature survey was conducted on herbs, their preparations and ingredients with reported liver protection activities, in which a total of 274 different species and hundreds of active ingredients have been examined. These ingredients can be roughly classified into two categories according to their activities: (1) the main ingredients, such as silybin, osthole, coumarin, glycyrrhizin, saikosaponin A, schisandrin A, flavonoids; and (2) supporting substances, such as sugars, amino acids, resins, tannins and volatile oil. Among them, some active ingredients have hepatoprotective activities (e.g. anti-inflammatory, anticancer, antioxidant, immunomodulating and liver cirrhosis-regulating effects). Calculation of physicochemical parameters indicates that the main ingredients with negative and positive E(lumo) values possibly display their hepatoprotective effects through different mechanisms, such as antioxidative, anti-inflammatory and immunomodulating effects. As the combination of herbs may achieve some treatment effects synergistically and/or additively, it is common in Chinese medicine to use mixtures of various medicinal herbs with pharmacologically active compounds to have synergistic and/or additive effects, or to reduce harmful effects of some pharmacologically active compounds. In particular, the active compounds with Clog P around 2 are suitable for passive transport across membranes and accessible to the target sites. Thus, E(lumo) and Clog P values are good indicators among the calculated parameters. Seven different physicochemical parameters (MW, Clog P, CMR, mu, E(lumo), E(lumo) and H(f)) and four major biological activities (antioxidant, anti-inflammatory, antiviral/antitumor and immunomodulating) are discussed in this review. It is hoped that the discussion may provide some leads in the development of new hepatoprotective drugs.
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