Mechanism of the ganglion-blocking action of bis-ammonium compounds

The action of polymethylene bis-ammonium compounds on acetylcholine-activated channels was investigated on voltage-clamped neurons of the isolated rabbit superior cervical ganglion. The kinetics of complex formation by the compound and the open channel was determined from shortening of decay of the fast excitatory postsynaptic current, the rate of which corresponds to the rate of channel closure, whereas the kinetics of dissociation of this complex was determined by recovery of the second response to application of two pulses of acetylcholine. With membrane hyperpolarization complex formation was found to be accelerated, and its dissociation retarded. The potential-dependence of interaction between compound and channel increases with lengthening of the polymethylene chain. Variation of one of the two cationic groups in a compound with a tetramethylene chain does not affect potential-dependence. In a series of bis-ammonium compounds, ganglion-blocking activity, determined on the cat superior cervical ganglionin situ was found to correlate with the velocity constant of binding with the open channel. It is concluded that the ganglion-blocking action of bis-ammonium compounds is determined by their channel-blocking activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 54–61, January–February, 1984.     

Identification of bis-quaternary ammonium compounds using mild ionization mass spectrometry

Ethonium, an antimicrobial chemotherapeutic agent, was investigated by mass spectrometry (MS) under various ionization conditions: electron impact, field ionization, field desorption (FD) and fast atom ionization. FDMS was found to be the most suitable procedure for ethonium identification. Relation of the ED mass spectra to the distance between the nitrogen atoms in bis-quaternary ammonium compounds is discussed. It was shown that the most intensive ions with m/z 499, 315 in the FD mass spectra corresponded to the ethonium specific fragmentation and their occurrence in the spectra could serve as a sufficient criterion useful in qualitative and quantitative assay of the drug in the sample.     

Mutagenic activity of selenium compounds.

The mutagenicities of selenate (SeO2/4-) and selenite (SeO2/3-) were determined by two bacterial assay systems: Kada's rec-assay and Ames's Salmonella test. In both assays, these compounds were found to be weak mutagens. In the Salmonella test, selenate (0.05 revertants/nmole) and selenite (0.2 revertants/nmole) gave rise to base-pair substitution.     

Factors affecting antibacterial activity of hop compounds and their derivatives.

The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.     

Biological activity of some steroidal compounds in the adult and larval frogs.

Four steroids were tested for their biological activity, using the sex-steroid-dependent redevelopment of the secondary sex characteristics in adult frogs and gonadal sex differentiation in larval frogs as end points. In adult frogs, 19-norprogesterone and 6-chloro-17alpha-hydroxy-4, 6-pregnadiene-3,20-dione had antiandrogenic and antiestrogenic effects. 2alpha, 17alpha-Dimethyl-DHT and 2alpha-methyl-DHT were potent androgens and effective antiestrogens. In the larval frogs, all four compounds had a masculinizing effect upon the undifferentiated gonads.     

The fungistatic activity of ethylenic and acetylenic compounds; the fungistatic activity of tetraiodoethylene and related compounds

The high fungistatic activity of tetraiodoethylene has been investigated. Diiodo-acetylene, which like tetraiodoethylene is an unsaturated substance containing only carbon and iodine, has also been found to have a high antifungal action. The effect of replacing the iodine atoms in these compounds by hydrogen, bromine, and carboxyl and nitro groups has been studied. The high fungistatic activity of some iodoethylenic and iodoacetylenic compounds appears to be associated with the presence in the molecule of positive iodine.     

Antifungal activity of new compounds from Nepeta leucophylla and Nepeta clarkei.

Iridodial beta-monoenol acetate, isolated from the essential oil of Nepeta leucophylla Benth, and actinidine from N. clarkei Benth were screened for antifungal activities against Aspergillus flavus, Aspergillus ochraceus, Penicillium citrinum, and Penicillium viridicatum, all known mycotoxin-producing taxa, and Sclerotium rolfsii and Macrophomina phaseolina, potential soybean pathogens. Iridodial beta-monoenol acetate was most effective against S. rolfsii, while actinidine was highly active against M. phaseolina.     

Thiono compounds. 4. In vitro mutagenic and antineoplastic activity of TEPA and thio-TEPA

Tris (1-aziridinyl) phosphine oxide (TEPA) and tris (1-aziridinyl) phosphine sulfide (thio-TEPA) induced base pair mutations in the Ames mutagenic assay. Thio-TEPA required metabolic activation while TEPA was active without metabolic activation. Growth of a human vaginal carcinoma (A431), a human breast carcinoma (MDAMB-231), and a human cervical carcinoma (HeLa) were inhibited in soft agar in vitro at concentrations which induced mutagenesis in the Ames Assay. A fourth line, JEG choriocarcinoma, was sensitive to the antigrowth properties of both drugs at concentrations below that which induced mutagenesis. These data suggest that as more antineoplastic agents become available, and as mean survival times increase, knowledge of the relative in vitro sensitivity of a patient's neoplasm to a specific antineoplastic drug (i.e., dose required for growth inhibition) as a function of its mutagenic index might be useful for prediction of clinical remission, as well as the risk of secondary neoplasm induction.Abbreviations TEPA tris (1-aziridinyl) phosphine oxide - thio-TEPA tris (1-aziridinyl) phosphine sulfide - MEM Minimal Essential Media This study was supported by PHS grant No. CA 30321 awarded by the National Cancer Institute (DHHS).