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PubMed1983

Pharmacological aspects of mianserin.

S(+)-mianserin is the more potent enantiomer of mianserin in pharmacological tests indicative for antidepressant activity. Pharmacological tests indicative for sedation suggest that sedative effects are similar for mianserin and its enantiomers. Racemic mianserin had the optimal therapeutic ratio of antidepressant-like activity versus sedative properties when assessed by computerised EEG in healthy volunteers participating in a double-blind placebo-controlled single dose trial. Of the known metabolites, desmethylmianserin and 8-hydroxymianserin substantially retain pharmacological properties indicative for antidepressant activity but are less active than mianserin in tests indicative for sedation. Mianserin-N-oxide is inactive or only weakly active in most pharmacological tests. Desmethylmianserin occurs in human plasma after both single and multiple dosage to an extent of about one-third that of mianserin. Mianserin has optimal clinical efficacy as the racemate. Desmethyl-mianserin and 8-hydroxymianserin are pharmacologically active metabolites and may contribute to the overall antidepressant effects of mianserin.

Adult↗
PubMed1988

Role of animal and human pharmacology in antifungal drug design.

Since the late sixties, several new antifungal drugs have become available. Initially, they were all intended for topical use, and, consequently, animal and human pharmacology always primarily aimed at confirming therapeutic efficacy. With the new tendency for the development of orally active antifungal drugs, human and animal pharmacology have significantly gained in importance. Indeed, not only is it now necessary to demonstrate the presence of adequate antifungal concentrations at the site of infection, but the systemic availability of the antifungal drug also necessitates an in-depth study of the effects of the drug on the function of several organs. As a result, human and animal pharmacology have become the cornerstones in the selection of orally active antifungal drugs. The development of ketoconazole has been an example of the need for optimized pharmacological screening. The choice of itraconazole--with its improved tissue affinity, its lower therapeutic dose requirements, and its increased selectivity for fungal cytochrome P-450--demonstrates very well that the use of animal and human pharmacology helps in the design of an antifungal drug with as much effect as possible on the fungus and as little effect as possible on the host.

Animals↗
PubMed2005

Pharmacological characterization of agonists at delta-containing GABAA receptors: Functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2.

Several groups have characterized the pharmacology of alpha4- or alpha6beta3delta-containing GABA(A) receptors expressed in different cell systems. We have previously demonstrated that the pharmacological profiles of a series of GABA(A) receptor agonists are highly dependent on the alpha subunit and little on the beta and gamma subunits, so to further understand the contribution of the different subunits in the GABA(A) receptor complex, we characterized a series of full agonists, partial agonists, and antagonists at alpha4beta3, alpha4beta3delta, and alpha6beta3delta receptors expressed in Xenopus oocytes. Little or no difference was seen when the compounds were compared at alphabeta- and alphabetadelta-containing receptors, whereas a significant reduction in both potency and relative efficacy was observed compared with alphabetagamma-containing receptors described in the literature. These data clearly confirm that the presence of the delta subunit in heterotrimeric receptors is a strong determinant of the increased pharmacological activity of compounds with agonist activity. The very similar agonist pharmacology of alphabeta- and alphabetadelta-containing receptors, which is significantly different from that of alphabetagamma-containing receptors, shows that whereas the presence of a gamma subunit impairs the response to an agonist stimulation of the alphabeta receptor complex, the delta subunit does not affect this in any way. Taken together, these data are well in line with the idea that alpha4beta3delta may contribute to the pharmacological action of exogenously applied agonists and may explain why systemically active compounds such as gaboxadol and muscimol in vivo appear to act as selective extrasynaptic GABA(A) agonists.

Animals↗
PubMed1998

Rat and human hippocampal alpha5 subunit-containing gamma-aminobutyric AcidA receptors have alpha5 beta3 gamma2 pharmacological characteristics.

The gamma-aminobutyric acid (GABA)A receptor is a hetero-oligomer consisting of five subunits, the combination of which confers unique pharmacological properties to the receptor. To understand the physiological role of native GABAA receptors, it is critical to determine their subunit compositions. The pharmacological characteristics of human alpha5 beta3 gamma2 and alpha5beta3gamma3 GABAA receptors stably expressed in L(tk-) cells were characterized with the alpha5-selective ligand [3H]L-655,708 and compared with the pharmacological characteristics of [3H]L-655,708 binding sites from rat and human hippocampus. Saturation analyses revealed a 9-fold selective affinity of [3H]L-655,708 for alpha5 beta3 gamma2 receptors (Kd = 1.7 +/- 0.4 nM), compared with alpha5 beta3 gamma3 receptors (Kd = 15 +/- 3 nM). Rat and human hippocampal [3H]L-655,708 binding sites had affinities of 2.2 +/- 0.6 and 1.0 +/- 0.2 nM, respectively, comparable to the affinity of alpha5 beta3 gamma2 receptors. Pharmacological analysis of [3H]L-655,708 binding sites in rat and human hippocampi revealed a strong correlation with the affinities of seven benzodiazepine site ligands for alpha5 beta3 gamma2 but not alpha5 beta3 gamma3 receptors. Immunoprecipitation of [3H]L-655,708 binding sites from rat hippocampus with a gamma2-selective antibody yielded 19 +/- 4% of total benzodiazepine binding sites measured using [3H]Ro15-1788, whereas no specific binding was measured after immunoprecipitation with an anti-gamma3 antibody. Combinatorial immunoprecipitations of [3H]muscimol binding sites with anti-alpha5 and anti-gamma2 or anti-alpha5 and anti-gamma3 antibodies established the preferential expression of alpha5 gamma2 receptors, accounting for 22 +/- 2% of total rat hippocampal GABAA receptors. These observations provide pharmacological and structural evidence for the prevalence of alpha5 beta3 gamma2 GABAA receptors in rat hippocampus, despite the clustering of alpha5 and gamma3 loci on the same chromosome.

Adult↗
PubMed2005

International Union of Pharmacology. XLVI. G protein-coupled receptor list.

NC-IUPHAR (International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification) and its subcommittees provide authoritative reports on the nomenclature and pharmacology of G protein-coupled receptors (GPCRs) that summarize their structure, pharmacology, and roles in physiology and pathology. These reports are published in Pharmacological Reviews (http://www.iuphar.org/nciuphar_arti.html) and through the International Union of Pharmacology (IUPHAR) Receptor Database web site (http://www.iuphar-db.org/iuphar-rd). The essentially complete sequencing of the human genome has allowed the cataloging of all of the human gene sequences potentially encoding GPCRs. The IUPHAR Receptor List (http://www.iuphar-db.org/iuphar-rd/list/index.htm) presents this catalog giving IUPHAR-approved nomenclature (where available), known ligands, and gene names for all of these potential receptors (excluding sensory receptors and pseudogenes) together with links to curated sequence, descriptive information, and additional links in the Entrez Gene database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene). This list is a major new initiative of NC-IUPHAR that, through continuing curation, defines the target of our ongoing receptor classification and invites further input from the scientific community.

Animals↗
PubMedDate not supplied

Pharmacologic interventions in nuclear radiology: indications, imaging protocols, and clinical results.

Nuclear radiology is valuable in assessing pathophysiology of a variety of organ systems. Pharmacologic interventions are often employed in radionuclide imaging to monitor the physiologic changes, which in turn facilitate the diagnosis. Metoclopramide, erythromycin, and cisapride have been used for gastric emptying studies. To overcome false-negative results, cimetidine, pentagastrin, and glucagon have been used in imaging of Meckel diverticula. Pharmacologic intervention with either cholecystokinin-8 or morphine is used primarily for the assessment of diseases of the gallbladder, common bile duct, and sphincter of Oddi. Pharmacologic interventions performed during renography include diuretic administration, angiotensin-converting enzyme inhibition, and aspirin renography. Recombinant thyrotropin can be used in patients with previously treated thyroid carcinoma who require lifelong follow-up for recurrent disease. Cardiac pharmacologic stress agents fall into two categories: coronary vasodilating agents, such as dipyridamole and adenosine, and cardiac positive inotropic agents, such as dobutamine and arbutamine. Measurement of hemodynamic responses to pharmacologic flow augmentation with carbon dioxide or acetazolamide is valuable in cerebrovascular perfusion studies.

Acetazolamide↗
PubMed1989

Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation.

The effect of daily exercise on the coronary resistance vessel sensitivity to intracoronary infusion of several pharmacological agents was assessed in 12 conscious adult mongrel dogs. alpha-Adrenergic receptor agonists (norepinephrine and phenylephrine) significantly decreased coronary blood flow velocity. beta 2-Adrenergic receptor agonists (isoproterenol and zinterol) and a metabolic vasodilator (adenosine) significantly increased coronary blood flow velocity. These responses occurred without altering factors that influence myocardial metabolism. Daily exercise significantly enhanced the coronary vascular sensitivity to each of the pharmacological agents. These results suggest that a nonspecific potentiation to pharmacological activation occurs after daily exercise. After left stellate ganglionectomy, intracoronary infusions of each pharmacological agent had similar effects on coronary blood flow velocity as presented for the intact dogs; however, daily exercise did not enhance the coronary vascular sensitivity to the pharmacological agents. These results demonstrate the need for an intact nervous system for the vascular adaptations associated with daily exercise.

Adenosine↗
PubMed2006

The cancer and leukemia group B pharmacology and experimental therapeutics committee: a historical perspective.

The Chemotherapy Committee of Cancer and Leukemia Group B (CALGB) was established in the mid-1970s to assemble a group of experts in cancer chemotherapy and pharmacology who could advise the CALGB disease committees about the optimal use of drugs in the fight against cancer and to provide quality assurance for the chemotherapy section of CALGB protocols. Chaired initially by Edward Henderson and then David Van Echo, the committee was also the repository of studies in diseases for which CALGB did not have a formal committee, such as testis cancer and sarcoma. In 1990, following the appointment of Richard Schilsky as Chair, the name of the committee was changed to the Pharmacology and Experimental Therapeutics (PET) Committee to reflect a more specific focus and scientific agenda (i.e., studies of chemotherapy pharmacology and development of new agents). Three PET Committee reference pharmacology laboratories (led by Merrill Egorin, Tony Miller, and Mark Ratain) were established to measure drug concentrations in biological fluids and to perform pharmacokinetic analyses. In addition, the PET Committee embarked on a number of multi-institution phase I studies. These phase I studies included studies of special populations, including the first prospective study of an anticancer agent (paclitaxel) in patients with hepatic dysfunction. In addition, the Committee studied a number of phase I combinations destined for phase II evaluation in disease-specific committees. Following Dr. Schilsky's election as CALGB Group Chair in 1994, Mark Ratain took over as Chair of the PET Committee and continued to emphasize population pharmacology as the primary theme of the Committee's research agenda. In addition, the PET Committee began to develop novel clinical trial designs, including the first completed randomized discontinuation trial of an antineoplastic agent. Most recently, the PET Committee has launched an ambitious research program in pharmacogenetics, facilitated in large part through the recruitment of Howard McLeod as Vice Chair. This area of research is a collaborative effort with the NIH Pharmacogenetics Research Network and has the potential to definitively address the hypothesis that germ line polymorphisms are a significant determinant of the toxicity and efficacy of anticancer therapy. It is anticipated that the results of the current studies will contribute significantly to the goal of individualizing cancer treatment.

Antineoplastic Agents↗
PubMed1975

Detection of latent function in acutely ischemic myocardium in the dog: comparison of pharmacologic inotropic stimulation and postextrasystolic potentiation.

In poorly perfused myocardium with resultant ischemic dysfunction, augmentation of contractility can, under certain conditions, be used to detect viable but ordinarily noncontracting muscle. Two methods of inotropic augmentation, pharmacologic inotropic stimulation and postextrasystolic potentiation (PESP), were studied in acutely ischemic canine myocardium with controlled coronary blood flow. A caliper length gauge to record segmental shortening and left ventricle pressure was used to construct pressure-length loops. Acute regional ischemia depressed segmental function: early segmental shortening decreased (-20 plus or minus 0.02% [SE]) and frequent dyskinesia occurred. Restoring coronary blood flow corrected segmental shortening to control levels. During acute regional ischemia, PESP consistently augmented segmental function (+49 plus or minus 0.03%) and abolished dyskinesia. Pharmacologic inotropic stimulation with isoproterenol or calcium administered into the coronary arteries did not produce a comparable improvement in segmental function (+9 plus or minus 0.05%). Although early shortening markedly increased with pharmacologic stimulation, there was no consistent change in total shortening, and the area of the pressure-length loop decreased. Due to late dyskinesia, there was a decrease in injection shortening. Systemically administered pharmacologic agents accentuated early dyskinesia but caused no consistent change in total shortening. Unlike PESP, pharmacologic agents either worsened segmental function or caused responses that were minimum and inconsistent; such responses clearly cannot be used to identify viable ischemic myocardium.

Acute Disease↗
PubMed1982

Dispersed human lung mast cells. Pharmacologic aspects and comparison with human lung tissue fragments.

The present investigation was designed to study the histamine release and pharmacologic characteristics of dispersed human lung mast cells, particularly in comparison with parenchymal tissue fragments. Dispersed human lung mast cells were prepared by enzymatic treatment (yield, 0.5 to 2 x 10(6) mast cells/g tissue). Purity was 1 to 8% (mean, 3.6% +/- 0.7%), and histamine content varied from 2 to 6 pg/cell (mean, 3.6 +/- 0.5 pg/cell). Release, studied using anti-IgE as the stimulus, was relatively rapid, being essentially complete within 15 min when high concentrations of anti-IgE (greater than or equal to 0.3 microgram/ml) were used and was not enhanced by phosphatidyl serine. The concentration of drug required to inhibit histamine release by 50% in dispersed cells for a series of pharmacologic agents, including the beta-adrenergic agent fenoterol, the prostaglandin E2, and the phosphodiesterase inhibitor isobutylmethylxanthine, were 0.1 to 1 microM, 50 microM, and 0.5 mM, respectively; similar results were obtained in simultaneous experiments performed using tissue fragments. Adenosine enhanced release (19 +/- 3.4%) at low concentrations (10 microM) and inhibited release (61 +/- 5.1%) at high concentrations (1mM). The H2 agonist, dimaprit (at 10(-5) to 10(-7) M) and prostaglandin D2 (at 10(-4) to 10(-6) M) had no effect on histamine release, whereas deuterium oxide potentiated histamine release. This study serves to quantitate the pharmacologic effects of several agents on anti-IgE-mediated histamine release from dispersed human lung mast cells and has further suggested that the dispersed cell system is similar to the standard chopped lung system in dose-response relationships, kinetics, and pharmacologic modulation. It also indicates that the enzymatic treatment of the cells does not affect the release characteristics or functional capacity of several different receptors, and that this preparation, therefore, appears suitable as an in vitro human model of mediator release that can be used for the evaluation of pharmacologic agents and for further mast cell purification.

1-Methyl-3-isobutylxanthine↗
PubMed2005

Comparisons between pharmacologically and Edinger-Westphal-stimulated accommodation in rhesus monkeys.

PURPOSE: Accommodation results in increased lens thickness and lens surface curvatures. Previous studies suggest that lens biometric accommodative changes are different with pharmacological and voluntary accommodation. In this study, refractive and biometric changes during Edinger-Westphal (EW) and pharmacologically stimulated accommodation in rhesus monkeys were compared. METHODS: Accommodation was stimulated by an indwelling permanent electrode in the EW nucleus of the midbrain in one eye each of four rhesus monkeys. Dynamic refractive changes were measured with infrared photorefraction, and lens biometric changes were measured with high-resolution, continuous A-scan ultrasonography for increasing stimulus current amplitudes, including supramaximal current amplitudes. Accommodation was then stimulated pharmacologically and biometry was measured continuously for 30 minutes. RESULTS: During EW-stimulated accommodation, lens surfaces move linearly with refraction, with an increase in lens thickness of 0.06 mm/D, an anterior movement of the anterior lens surface of 0.04 mm/D, and a posterior movement of the posterior lens surface of 0.02 mm/D. Peak velocity of accommodation (diopters per second) and lens thickness (in millimeters per second) increased with supramaximal stimulus currents, but without further increase in amplitude or total lens thickness. After carbachol stimulation, there was initially an anterior movement of the anterior lens surface and a posterior movement of the posterior lens surface; but by 30 minutes, there was an overall anterior shift of the lens. CONCLUSIONS: Ocular biometric changes differ with EW and pharmacological stimulation of accommodation. Pharmacological stimulation results in a greater increase in lens thickness, an overall forward movement of the lens and a greater change in dioptric power.

Accommodation, Ocular↗
PubMedDate not supplied

Pharmacologic management of postdural puncture headache.

OBJECTIVE: To discuss the pathogenesis, incidence, and clinical presentation of postdural puncture headaches (PDPHs) and to provide a comprehensive evaluation on the pharmacologic management of PDPH. DATA SOURCE: A MEDLINE search was used to identify pertinent literature published in English including review articles, case reports, letters, and abstracts. Information was also extracted from textbooks for background purposes. STUDY SELECTION: All clinical studies, case reports, abstracts, and letters were included because of the limited amount of literature available on the pharmacologic therapy for PDPH. Related research articles and review articles were also used to provide background information on PDPH. DATA EXTRACTION: Methodology and results from clinical trials and abstracts were described and evaluated. Case reports and letters were summarized and critically reviewed for the feasibility of the different treatment modalities. Information on the pathophysiology, incidence and severity, and clinical presentation of PDPH was extracted from related research articles, review articles, and textbooks. DATA SYNTHESIS: The epidural blood patch (EBP) is one of the most effective treatments for PDPH. Pharmacologic management of PDPH offers a less invasive treatment modality than the EBP. Numerous drug therapies have been presented in the literature, though few merit clinical application. Caffeine therapy, both oral and parenteral, is the most commonly used pharmacologic treatment modality. Theophylline and sumatriptan are potentially promising agents for the treatment of PDPH. Epidural administration of fluids and drugs is also effective in the treatment of PDPH. Epidural adrenocorticotropic hormone and epidural morphine also demonstrate some potential in the treatment of PDPH. Individual patient characteristics (i.e., HIV, sepsis) need to be considered when deciding on a treatment. More reports, especially clinical studies, are necessary before a definitive statement can be made regarding any one treatment. In the meantime, therapy will be guided by clinical judgement based on the literature reviewed in this article. CONCLUSIONS: Intravenous and oral caffeine are effective and noninvasive treatments for PDPH. Epidural NaCl 0.9% or dextran are alternatives when the EBP is unsuccessful or contraindicated. Several methods of pharmacologic management have been cited in the literature, but all require further evaluation.

Administration, Oral↗
PubMed1990

Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation.

The purpose of this study was to compare the reproducibility of two approaches to the evaluation of GH secretion: the integrated concentration of GH (IC-GH), a physiological test of GH secretion, and pharmacological stimulation tests. IC-GH was determined in 40 poorly growing children twice within 4 weeks. The first and second IC-GH were highly correlated r = 0.859, P less than 0.001. One hundred and thirteen poorly growing children underwent pharmacological GH stimulation tests twice within 6 weeks. A moderate correlation was found between the first and second pharmacological test r = 0.524, P less than 0.01. Among the three pharmacological stimuli studied, clonidine (n = 81) had the highest reproducibility followed by arginine (n = 20), and insulin (n = 12). We conclude that IC-GH is more consistently reproducible than the GH response to repeated pharmacological stimulation.

Adolescent↗
PubMed1995

The relationship between the pharmacological effect of amitriptyline based on an improved forced-swimming test and plasma concentration in rats.

The relationship between the plasma concentration of amitriptyline (AMI) and its pharmacological effect was investigated in rats. The plasma concentration of AMI was maintained constantly from 5 h to 7 d after intraperitoneal infusion by the implantation of an osmotic minipump with an adjusted release rate of 20 mg/kg/d of AMI. Neither the plasma or brain concentrations of AMI in a 24-h infusion group were significantly different as compared with those in the 7-d group. The pharmacological effect of AMI was measured by our improved forced-swimming test. When AMI (dose of 20 and 50 mg/kg/d) was infused, the pharmacological effect in both infusion groups of rats was increased significantly at each dose in comparison to that of the control rats (p < 0.05). With 10 mg/kg/d infusion, the effect in the 7-d group increased significantly as compared with that of the control (p < 0.05), although the effect in the 24-h group did not change. The effect was increased in both groups with an increase of dose. When the effect was plotted to the area under the plasma concentration-time curve (AUC), the effect approached a limiting value (12 micrograms/ml.h). Therefore, it was suggested that 12 micrograms.ml/h as the AUC for AMI was enough to obtain a maximum AMI pharmacological effect in rats. From these results, we concluded that the AUC for AMI may be a useful index to evaluate its pharmacological effect, rather than the plasma concentration.

Amitriptyline↗
PubMed2006

Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions.

The multiple pharmacological actions of a unique compound are a prerequisite for classifying drugs as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various symptoms of chronic diseases as described below. 1) Sustained hyperglycemia induces macrovascular and microvascular complications in type 2 diabetes mellitus. Antihyperglycemic medication and the control of postprandial hyperglycemia are essentially important for normalizing plasma glucose level. Gymnemic acid IV isolated from Gymnema sylvestre (Asclepiadaceae) leaves has antisweet, antihyperglycemic, glucose uptake inhibitory, and gut glycosidase inhibitory effects. Most of these pharmacological effects may synergistically contribute to alleviating type 2 diabetes-related symptoms. 2) Diabetic skeletal and vascular smooth muscles are hypersensitive to chemical transmitters, cytokines and autacoids. The sensitivity of neuromuscular synapses is enhanced in diabetes, which seems to be closely associated with neuropathy as one of the diabetic complications. beta-Eudesmol found in Atractylodes lancea rhizome has a desensitizing channel blocking action to nicotinic acetylcholine receptors, anti-angiogenic action in vascular endothelium, and neuronal differentiation actions. These multiple pharmacological actions are favorable for treating angiogenic diseases possibly including the complications of diabetes, namely, retinopathy and nephropathy, and cancer. 3) Nipradilol is clinically utilized as a topical antiglaucoma drug. The ocular hypotensive effects of this compound are brought about by its alpha1 and beta-adrenergic receptor blocking actions, and nitric oxide (NO) releasing action. NO directly activates cyclooxygenases. All these pharmacologic effects are beneficial for treating glaucoma. The selectivity and specificity of drug action are required for treating acute diseases, infections or for acting as useful reagents. The pleiotropic actions of natural compounds and their derivatives serve as important clues for developing new drugs for various chronic diseases.

Adrenergic Antagonists↗
PubMed1996

[Aspect of patho-receptor in the modern pharmacology for drug design developing from Japanese traditional sino-medicines systems].

This article is a summary of the molecular patho-pharmacological studies continuously investigated for more than 30 years in Toyama Medical & Pharmaceutical University. The aim of this study was to develop the motivation and the strategy for the original drug-design by targeting the pharmacological mechanism of receptor modified by the pathological state in the animal models for the diseases, followed by searching the pathoreceptor-sensitive drugs as a probe of new medicines. The drug activity consists of two factors, affinity and intrinsic activity to the receptor, depend on their chemical structures of supporting moiety and radical moiety, respectively. The former can be discovered from the natural products, composing Japanese traditional Sino-medicines, and the later can be modified by chemical synthesis. By using this strategy, several new findings, a large number of new compounds and/or new pharmacological activity, were obtained as follows: I. On the molecular pharmacology of nicotinic ACh receptor. II. On the development of new drugs affecting on smooth muscle. III. On the pathopharmacological investigation with a model of diabetic mice. IV. On the applied pharmacology of Japanese traditional Sino-medicines.

Animals↗
PubMed1997

[The molecular patho-pharmacological studies for novel drug design by a principle of drug action in Japanese traditional Sino-medicine system].

In this study we carried out the pharmacological elucidation of the principle of drug action in the Japanese traditional Sino-medicine system, which could have contributed to the modern pharmacology and therapeutics through the discovery of a novel drug design and a new mechanism of drug action. The aim of this study was to focus on the elucidation of the supporting moiety in the drug design for the drug having affinity for a patho-receptor using a quite unique strategy and a new approach based on the natural products, Japanese traditional Sino-medicines relating to disease state, because of enormous clinical experiences with a long history. The characteristics of the pharmacological effects of Japanese traditional Sino-medicines were experimentally demonstrated by the following three key compartments, 1) the combined effect of drugs, 2) the selective activity of drugs to the disease state, 3) the possibility of individual symptomatological patterns (sho) evaluated by autonomic and immuno-pharmacological components. The success of the investigation on the principle of drug action of Japanese traditional Sino-medicines induced not only to obtain many novel compounds and unknown new mechanisms of drug action, but also to find a new salivary peptide for anti-hyperglycemics and a fresh mechanism of ACh receptor desensitization in neuromuscular synapse in the modern pharmacology. The results have brought the interchangeability of Japanese traditional Sino-medicine system to modern medicinal sciences, as described in the following contents, I. On the elucidation of a principle of drug action in the Japanese traditional Sino-medicine system. II. On the developmental frontier of drug design based on Japanese traditional Sino-medicines. III. On the interchangeability between the Japanese traditional Sino-medicine system and the modern medicinal sciences.

Animals↗
PubMed1999

Pharmacologic considerations for therapeutic success with antiretroviral agents.

OBJECTIVE: To explore pharmacologic elements that contribute to therapeutic success with agents used for the treatment of HIV infection. DATA SOURCES: Primary articles were identified through MEDLINE (January 1990-January 1999) and secondary sources. Conference abstracts were selected by review of published proceedings. STUDY SELECTION AND DATA EXTRACTION: The author evaluated all articles, and relevant information was selected for incorporation into this review. DATA SYNTHESIS: Heterogeneity in the response to antiretroviral therapy has been attributed to virologic, immunologic, behavioral, and pharmacologic differences among patients. Patients receiving the same dose of an antiretroviral agent will not have the same systemic or intracellular concentration because of interpatient variability in drug absorption, distribution, metabolism, and excretion. Pharmacologic theory and available clinical data support relationships between drug concentration and anti-HIV effect. Thus, variability in drug concentrations contributes to variability in antiviral effect. Desirable pharmacologic characteristics for an antiretroviral drug include high oral bioavailability, a long elimination half-life, low intra- and interpatient pharmacokinetic variability, and a predictable dose-concentration-effect relationship. CONCLUSIONS: Treatment of the individual who is infected with HIV is a challenging long-term undertaking. Optimal management requires synthesis of a rapidly evolving base of basic and clinical knowledge. The selection of an antiretroviral regimen based on an understanding of the degree to which each individual agent possesses the desired pharmacologic characteristics should help the healthcare provider to translate the therapeutic principles of treatment of HIV infection into clinical reality for all patients.

Anti-HIV Agents↗