Rifamycin SV in the Treatment of Knee Synovitis.

Rifamycin SV, injected intraarticularly at dosages of 500 mg weekly, induced a complete removal of persistent knee effusions in 57 of 60 rheumatoid patients, and in all patients with effusions due to juvenile rheumatoid arthritis (three), ankylosing spondylitis (three), psoriatic arthritis (10), intermittent hydrarthrosis (two) and chondromatosis (two). One rheumatoid patient did not respond to treatment, and two dropped out because of local side effects. The number of infiltrations varied between three and 12, and was correlated with activity grade of local synovitis (P < .05). As of this writing, 50 out of 57 rheumatoid patients and 19 out of 20 belonging to the other groups have not had a relapse of effusions after 25 to 36 months and 12 to 20 months respectively. While the changes in the synovial fluid and membrane of the rheumatoid subjects, and the results obtained from experimental arthritis in guinea pigs, confirm the hypothesis that Rifamycin has a local antiinflammatory action in arthritic knee joints, they also suggest that this property alone of the drug is not entirely responsible for its therapeutic action.

[Quantitative evaluation methods of the chemoantibiotic associations (author's transl)]. / Metodi di valutazione quantitativa delle associazioni chemioantibiotiche.

In the introductory part a new classification of joint drug actions is submitted, according which three fundamental types are distincted, named respectively interference, cooperation and true interaction. In its turn, interaction is subdivided in three classes (uni-effectual, bis-ineffectual, bis-effectual) in the last of which is placed the most relevant of the interactions, that is synergism, subclassified, at its turn, as additive, super and infra-additive. The second part is devoted to the classification of the bacteriological techniques hitherto proposed in order to evaluate in vitro and in vivo the antibacterial interaction of chemoantibiotics. The third part is devoted to the classification and critical analysis of biometrical techniques hitherto applied to above quoted bacteriological techniques in order to obtain a quantitative evaluation of interaction. Criticism versus isobolic model is pointed out. In the final part a new procedure, named isoeffectual, is proposed. According to such a procedure a close grid of single and joint concentrations of a couple of chemoantibiotics, broad enough in order to cover the whole of the effects to be explored, is tested in vitro adopting the one-center agar diffusion test or a liquid medium. The experimental data so obtained are related in a planar diagram to the log of the sum obtained by adding to the concentrations of the first the concentrations of the second agent, converted into equi-effectual concentrations of the first. By this way a series of curvilinear regressions is obtained, which may be all explained by a mathematical formula according which the data may be submitted to statistical analysis and elaborated in order to draw the parameters able to define quantitatively the interaction. The model so applied is discussed as a general model for joint drug action.

The psychopharmacological properties of pinazepam, a new benzodiazepine derivative.

The pharmacological differences between the behavioural effects of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) and diazepam were investigated in rats. Pinazepam was more than twice as active as diazepam at a dose range between 1.25--10 mg/kg in reducing the conditioned emotional response (CER). Only at doses of 2.5 and 5 mg/kg prevented pinazepam the disruption of the avoidance responses induced by inverting the conditioned stimulus (CS). On the other hand pinazepam was less active than diazepam in reducing the number of avoidance responses in a conditioned avoidance situation. Neither pinazepam nor diazepam disrupted the conditioned responses in a fixed-interval operant behaviour.

Pharmacological properties of the anti-inflammatory agent pyridyl-biphenylyl-acetamide (diphenpyramide).

Pyridyl-biphenylyl-acetamide (diphenpyramide, Z-876) is a new bisphenylalcanoic derivative with marked anti-inflammatory, analgesic, antipyretic and uricosuric properties. It is more active than phenylbutazone in the adjuvant polyarthritis in the rat when given prophylactically or therapeutically. It is thrice as active as phenylbutazone and ten times as active as acetylsalicylic acid (ASA) on the carrageenin-induced edema of the hind-paw. Diphenpyramide is characterized by low acute toxicity and by weak ulcerogenic activity. On the carrageenin-induced edema the therapeutic index of diphenpyramide is 30 times higher than that of indometacin and the ratio between the ED50 and the UD50 (ulcerogenic dose in 50% of the treated rats) is 39 times higher than that of ASA.

Serum kinetics and urinary metabolism of dimethophrine in rat.

The serum kinetics and urinary metabolism of an a-sympathomimetic amine 1-(3,5-dimethoxy-4-hydroxyphenyl)-2-monomethyl-amino-ethanol (dimethophrine) were studied. For serum kinetics, seven groups of 6 rats were sacrificed at 0.083, 1, 2, 2, 4, 6 and 12 H, respectively, after tail administration of dimethophrine-7-3H. Only 1 group of 6 rats was placed into metabolism cages to collect urine at 12-h intervals during the 72 h after dimethophrine-7-3H administration as above. The metabolic identification was made by thin-layer chromatography (TLC) and the radiochromatograms were obtained by the "scraping" method. This work shows dimethophrine to be unchanged in the urine of rat.

Toxicological and pharmacological investigations of pinazepam (7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one): a new psychotherapeutic agent.

The pharmacological and toxicological properties of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) were investigated and compared with those of diazepam. In mouse and rat acute toxicity, in rat motor coordination and in rat metrazol convulsion tests pinazepam was compared with oxazepam too. Pinazepam, which is characterized by the presence of a propargylic side chain, showed a lower toxicity, hypnotic activity and muscular-relaxant activity than diazepam. Pinazepam and diazepam showed, however, similar activity in reducing aggressive behaviour in mice, stimulating the exploratory behaviour in rats and in potentiating hexobarbital narcosis. No clear-cut differences were observed in the anticonvulsant properties of the two drugs when tested against metrazol, strychnine and electroshock induced seizures. Pinazepam differs from diazepam for its longer duration of action. The main metabolic product found in the urine of rats and dogs treated with pinazepam was oxazepam.