Showing papers in "Advances in pharmacology in 1978"

Suramin: with special reference to onchocerciasis.

Abstract: Publisher Summary This chapter discusses the suramin with special reference to onchocerciasis. Suramin is a pinkish white flocculent powder, with high solubility in water (more than 10% w/v); its solutions are stable to boiling. Suramin is hygroscopic and absorbs moisture from the atmosphere unless kept in a desiccator; the presence of this unsuspected water may cause errors in quantitative experiments. The capacity of suramin to combine with the plasma proteins depends on the naphthylaminetrisulfonic groups. Many of the pharmacological properties of suramin, e.g., its binding to serum proteins are because of its general structure as a large molecule with many sulfonic acid groups. Suramin forms complexes with serum proteins and is then taken up into lysosomes where it accumulates, just as acidic vital dyes do. This accumulation occurs in the reticuloendothelial cells all over the body but particularly in the Kupffer cells of the liver and in the cells of the convoluted tubules of the kidney. Suramin (which has six acidic groups) combines with basic compounds such as pentamidine and homidium to give insoluble complexes that are less toxic than the parent compound. They are deposited at the site of injection and are slowly absorbed, producing prophylaxis against trypanosomes over long periods.

Pharmacology and neurochemistry of apomorphine.

Abstract: Publisher Summary This chapter discusses the pharmacology and neurochemistry of apomorphine. Apomorphine was first employed as a powerful emetic agent. Apomorphine can be obtained by the acid-catalyzed rearrangement of morphine and by total synthesis. The hydrochloride forms colorless crystals that readily undergo superficial oxidation and assume a greenish tinge. Apomorphine solutions in water are unstable, turning green upon exposure to light and to air oxygen. Oxidation of apomorphine is much slower in acidic media. These properties of apomorphine explain the current addition of ascorbic acid to apomorphine solutions. The preparation of apomorphine by the acid-catalyzed rearrangement of morphine results in the retention of the configuration at the C6a chiral center leading to the corresponding (–)-isomer. Apomorphine has been measured in biological samples by spectrophotometric and fluorimetric methods and by fluorescence quenching after chromatographic separation. Apomorphine is metabolized by O-glucuronidation, O-methylation, and, probably, by N-demethylation. Apomorphine is methylated in vitro when incubated with rat liver soluble fraction in the presence of S-adenosylmethionine as methyl donor. This reaction is carried by the enzyme COMT.

Daunomycin: an anthracycline antibiotic effective in acute leukemia.

Abstract: Publisher Summary Daunomycin is an antitumor antibiotic of the anthracycline group, which was isolated in the Farmitalia Research Laboratories in Milan, Italy, from cultures of Streptomyces peucetius. The major part of the drug was found in the culture media of the mycelium and was isolated by means of solvent extraction, cation resins, and paper or column chromatography. The yield was 5–15 mg of product per liter of culture media. The soil sample was from Castel del Monte, near Puglie, and hence the name of the species S. peucetius. The drug is classified as an anthracycline and has similar physicochemical characteristics to rhodomycins, cynerubines, pyrromicins, and rutilantines. Daunomycin consists of a pigmented aglycone (daunomycinone) in glycoside linkage with an amino sugar (daunosamine). Daunomycin inhibits the multiplication of bacteriophage. It strongly inhibits DNA phages by acting during the replication cycle of the phage and not on absorption, injection, or lysis. The RNA phage growth was unaffected by daunomycin. The antiphage activity was proportional to the concentration of daunomycin. The antiphage activity was partially blocked by DNA but not by nucleotides or nucleosides.

Structural requirements for tetracycline activity.

Abstract: Publisher Summary This chapter discusses the structural requirements for tetracycline activity. Chlortetracycline, the first member of the tetracycline group to be discovered, was first isolated from Streptomyces aureofuciens during a systematic screening of microorganisms for antimicrobial products and was followed by the isolation of oxytetracycline from Streptomyces rimosus. Tetracycline, the parent member of the group, was initially prepared by reductive hydrogenolysis of chlortetracycline and subsequently by fermentation. These three antibiotics possess essentially equivalent antibacterial activities. The tetracyclines contain two distinct π-electron systems: the phenoldiketone moiety and the tricarbonylmethane moiety; these are independent because of the presence of the interposed 12a-hydroxy group. Both of these chromophoric groups must be retained intact otherwise activity is lost. Loss of activity, therefore, results from cleavage of one of the rings or from aromatization of the A or C ring or from modification of the phenoldiketone moiety by 11a-substitution or by deletion of the 12a-hydroxy group. It is, therefore, inferred that a compound must contain these groups otherwise it will not possess tetracycline-like activity.

Neurotransmitter mechanisms during mental illness induced by alterations in thyroid function.

Abstract: Publisher Summary This chapter discusses the neurotransmitter mechanisms during mental illness induced by alterations in the thyroid function. Data demonstrate that depressed behavior and mental deficit seen in thyroid-ablated animals might be associated with decreased synthesis and turnover of brain NE, DA, and 5-HT as well as an increased accumulation of acetylcholine and ratio of ACh to DA. By contrast, behavioral excitability seen in neonatally hyperthyroid rats may be associated with enhanced activity of noradrenergic, dopaminergic, and 5-hydroxytryptaminergic neurons in the brain. Further, cholinergic activity was enhanced contradicting the hypothesis that an increased ratio of DA to ACh is responsible for enhanced motor activity. Unlike Parkinson's disease or Huntington's chorea, hyperthyroidism is not generally associated with qualitative changes in motor performance, and it is probable that simultaneous increases in cholinergic and dopaminergic functions (without marked alterations in the ratio of these putative neurotransmitters) would only produce quantitative changes in spontaneous locomotion. Thyroid hormone administration in mature animals failed to exert any significant effect on the locomotor activity as well as on TH and TPH enzymes that regulate the biosynthesis of catecholamine and 5-HT, respectively.

Immune modulation and cancer control.

Abstract: Publisher Summary This chapter discusses immune modulation and cancer control. Cytotoxic responses may be prevented at several levels of the immune reaction. If the tumor is non- or only weakly antigenic, the immunologically specific response may be absent or too weak to be effective, particularly in the presence of immunosuppressive factors. It is assumed that the tumor is antigenic and that specific tumor-directed immunity is present. The most conclusive proof for effective in vivo killing of the tumor cells may require the demonstration of cytotoxic reactivity using the patient's own serum and tumor cells or patient's lymphoid or other effectors and tumor cells. The correlation between in vitro cytotoxicity and in vivo effects at a particular time may not be precise or may be absent because of other factors contributing to tumor regression (e.g., chemotherapy, other treatments), and also because of the time lag between either tumor regression and the disappearance of blocking factors from the serum (or other body fluid) or between the occurrence of blocking factors and tumor progression as estimated clinically. Correlation between the result of cytotoxic tests and the clinical regression may thus require repeated tests. Conversely, increased inhibitory activity might precede the clinical progression of the tumor.

Drug information services.

Abstract: Publisher Summary The essential aim of drug information is to encourage the appropriate use and to discourage the inappropriate use of drugs. In operation since 1971, MEDLINE (MEDLARS on-line) is the sophisticated outgrowth of the MEDLARS (Medical literature Analysis and Retrieval System) searching system that operated in a batch mode so effectively from 1966 to 1971. MEDLINE, a data base that was built and is maintained by the National Library of Medicine, contains references to more than 2.6 million citations from approximately 3000 worldwide biomedical journals. The data base begins in 1966 and is made up of a series of 3-year segments, each separately searchable. Access to MEDLINE is afforded by a variety of typewriter-like terminals connected to computers either in Bethesda, Maryland, or in Albany, New York, using ordinary telephone lines and the nationwide TYMNET or TeleNet communications networks. The MEDLINE service is available at more than 500 medical libraries, medical schools, government agencies, and companies in the United States, as well as at locations in Canada, the United Kingdom, France, Mexico, Iran, the World Health Organization in Geneva, South Africa, and Sweden.