Iproniazid was found to inhibit formalin-induced oedema of the foot, dextran-induced oedema and cotton-pellet-induced granulomatous tissue in the rat. The presence of the adrenals was essential for the antiphlogistic activity. The antiphlogistic action was not accompanied by any antipyretic effect. Inhibition of formalin-induced oedema was also observed with phenylbutazone and with salicylamide.Little is known about the therapeutic efficacy and mechanism of action of iproniazid in rheumatoid arthritis. In the opinion of Scherbel (1957, 1958a and b), the main effect of the drug is to improve the psychic condition of patients. However, Banghart (1958), using *higher doses, frequently obtained objective improvement, but he also observed side-effects in a large number of patients and frequently had to reduce the dose or even suspend treatment with the drug. This paper describes a pharmacological investigation of the mechanism of action of iproniazid in artificially induced inflammatory states. METHODS Antiphlogistic ActionFormaldehyde-induced Oedema. -Oedema was induced in the hind foot by the injection of 0.1 ml. of a 3% solution of formaldehyde into the plantar aponeurosis of male rats (150 to 250 g. Cotton-pellet-induced Granulomata.-The weights of the granulomata, which formed after the subcutaneous insertion of cotton pellets weighing 18 lo 19 mg. into male rats weighing 70 to 80 g., were estimated by the method of Meier, Schuler, and Desaulles (1950). Administration of iproniazid was started the day after implantation, and either 50 or 100 mg./kg. of the drug was given subcutaneously daily for six days. On the eighth day after implantation the rats were killed, the granulomata removed, freed from the cotton nucleus and wetweighed. Antipyretic ActionThis was tested by the subcutaneous injection of the drugs into rabbits which received immediately afterwards an intravenous injection of 1 ml. of antityphoid vaccine mixed with 1 ml. of a 20% suspension of brewers' yeast. Rectal temperatures were measured by thermocouples. RESULTSFormaldehyde-induced Qedema. Iproniazid in doses of 200( mg. /kg. almost completely inhibited a formaldehyde-induced oedema (Fig. 1). With doses of 100 and 50 mg./kg., the inhibition was less marked but statistically significant. The intensity of the antiphlogistic action was expressed quantitatively by measuring the area enclosed between the curves for the control and treated animals ( Figs. 1 and 2). The logarithm of the dose and the surface (expressed in arbitrary units) of these areas are clearly proportional (Fig. 3).The antiphlogistic effects of phenylbutazone and salicylamide are represented in Fig. 2

A series of 5-nitro-2-furaldehyde aminoacethydrazones, synthesized in our laboratories are screened in vitro and in vivo for antibacterial activity. Because of its good antibacterial activity against gram-negative and gram-positive organisms, its good absorption and its exretion in high urinary levels in active form, the 5-nitro-2-furaldehyde 4’-methylpiperazinoacethydrazone (Rec. 15-0122, nifurpipone) was selected for further studies.

The activity in vitro of tibezonium (Rec 15–0691), a new 1,5-benzo-diazepine derivative, has been investigated. The drug was found active especially against Streptococcus, Diplococcus and Corynebacterium strains which are agents of oropharyngeal diseases. The activity of tibezonium was pH dependent against Staphylococcus aureus SG 511 and Streptococcus pyogenes 821 (at pH 8.0–8.5 it was more active) and the presence of horse serum provoked a small decrease of the antimicrobial properties. No interference on the activity of the tibezonium has been found in presence of smokers and non-smokers saliva.

From a series of 5-nitro-2-furaldehyde amicoacethydrazones, 5-nitro-2-furaldehyde N′-methyl-N-piperazinoacethydrazone (nifurpipone, Rec 15-0122) was chosen for further studies. The in vitro antibacterial spectrum of this new water-soluble nitrofurane derivative corresponds to that of nitrofurantoin included in this study for comparison. Beside the solubility in water, there is a fundamental difference in pH-depend-ence of in vitro activity. Nifurpipone is more active at alcaline pH whereas nitrofurantoin is more active at acid pH.

Dimercapto‐propen‐one (I) reagieren mit o‐Phenylendiamin (II) zu den Benzodiazepinthionen (III), welche mit den Chloriden (IV) alkyliert werden können.