Acta pharmaceutica Nordica最新文献

Adrenaline injection fluids aged between 3 and 33 years were analyzed with respect to oxidation and racemization. The oxidation was determined by ion-pair reversed phase HPLC, and the degree of racemization was determined by derivatization of the adrenaline isomers to diastereomeric forms and subsequently separated by reversed phase HPLC. 10% adrenaline was oxidized after about 11 years, while 10% L-adrenaline was converted to D-adrenaline after only 4 years. After about 4 years, the injections contained less than 90% active adrenaline.

1,4-Benzodiazepines in solution accommodate two chiral conformations. Two closely related quartets following the substitution pattern: 3-unsubstituted, 3S-methyl, 3R-methyl, 3,3-dimethyl, were synthesized and the binding strength of the compounds to the benzodiazepine receptor was tested. The intertwining effects of (i) conformational preference of free molecules, (ii) conformational recognition by the receptor, and (iii) axial and equatorial methyl substituents, were separated by computation. It is concluded that conformation M enriched by 3S-methyl and impoverished by 3R-methyl enantiomers is recognized by the receptor, whereas the binding is strongly and moderately hindered by axial and equatorial methyl substituents, respectively.

The biochemical and pharmacological profiles of R,S-fluoxetine and its R and S enantiomers have been compared and reviewed. Both enantiomers exhibit profiles analogous to R,S-fluoxetine as inhibitors of serotonin uptake in vitro and in vivo with about equal potencies or a eudismic ratio near unity.

About 200 samples of normal saline, isotonic glucose and Ringer acetate infusions in soft polyvinyl chloride (PVC) bags obtained from three manufacturers have been analyzed by conductometric particle counting, turbidimetry and gas liquid chromatography (GLC). The particle counts were fitted to an exponentially modified log-normal model and integrated for total particle-volume. Di(2-ethylhexyl) phthalate (DEHP) and epoxidized vegetable oils (EVO), which are the main water insoluble contaminants in PVC fluid bags, were determined by GLC. There was a strong linear correlation between turbidity and GLC results. The correlation between particle-volume concentration and the DEHP and EVO concentrations was fairly good. The results seem to verify that an emulsion of plastic additives is formed when soft PVC infusion fluid bags are shaken.

New indole derivatives and their intermediates were tested as cytotoxic agents on a culture of P388 leukemia cells. The aldehyde 2a was more active than the thiosemicarbazones 3a, b and the nitrosourea 14. The chloroacetyl derivatives 10, 11 were the most potent cytotoxic agents.

The stereochemical complexity of roflamycoin and other polyene macrolide antibiotics presents a formidable challenge to the synthetic chemist, and the lack of obvious disconnections makes the retrosynthetic analysis very complex. The alternating (1, 3, 5, ...) polyol chain in roflamycoin is difficult to synthesize in part because there is no simple method to assemble these chains from smaller subunits. We have addressed this problem and developed a simple, convergent method for assembling alternating polyol chains. It is designed around a new class of 1,3-diol synthons: 6-alkyl-4-thiophenyl-1,3-dioxanes. These 1,3-diol synthons are readily available from either homoallylic alcohols or beta-hydroxyesters, which are themselves readily prepared in optically pure form. Reduction of these synthons under the appropriate conditions gives configurationally stable alkyllithiums with either syn or anti stereochemistry. Reaction with electrophiles produces protected syn or anti-1,3-diols.

The distribution of toxic pyrrolizidine alkaloids in the Icelandic flora has been studied for the first time. In addition to the isolation of senecionine, seneciphylline, and retrorsine from Senecio vulgaris L., the presence of riddelline was confirmed by high resolution NMR spectroscopy. The presence of this alkaloid in S. vulgaris has previously been controversial. Furthermore, senecionine oxide and seneciphylline oxide were isolated by preparative centrifugal chromatography.

A synergistic effect of clotrimazole and certain anionic surfactants against a strain of Candida albicans was confirmed. Measurement of apparent partition coefficients indicated that lipophilic ion pairs between clotrimazole and anionic surfactants were formed. It is suggested that the synergistic effect of the drugs may be due to ion pair formation.

A diffusion cell with an artificial membrane (dialysis membrane) was used to study the in vitro release of antralin from an o/w cream (Locobase) in the presence of salicylic acid. The concentration range of antralin was 0.04-3.0%. The influence of salicylic acid on the in vitro release was studied by adding 0.5-3.0% salicylic acid to the creams. Addition of salicylic acid improves the solubility of anthralin in water and probably also in the aqueous phase of the cream. It may also have an effect on the microviscosity of the cream as the structure of the cream changes. Both these factors promoted the in vitro release of antralin. There was also an improvement in clinical efficacy when salicylic acid was added. In this case, the results also can be explained by an isolated effect on the permeability of the stratum corneum.

A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N-benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N-butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline-1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations.