Synthesis and biological activities of the tri-L-alanine derivative of isonicotinic acid hydrazide

N-(tert-Butyloxycarbonyl) tri-L-alanine was coupled to the hydrazide function of isonicotinic acid hydrazide followed by cleavage of the amino protective group. The resulting dihydrochloride of the tri-L-alanine derivative of isonicotinic acid hydrazide was characterized by 13C-NMR. The minimal inhibitory concentration of isonicotinic acid hydrazide was not improved by the peptide derivative, and competition experiments with tri-L-alanine demonstrated that tri-L-alanyl-isonicotinic acid hydrazide did not use the peptide transport system. Isonicotinic acid hydrazide and its tri-peptide derivative possessed the same activity against pathogenic mycobacteria and did not antagonize each other. The relatively high stability of the tri-peptide derivative against peptidases of Mycobacterium fortuitum was discussed as being responsible for the significantly weaker activity against this atypical mycobacterium strain. With the exception of peptidases of hog intestinal mucose, the tri-L-alanyl derivative of isonicotinic acid hydrazide was stable to pronase and alpha-chymotrypsin when compared to other peptides.     

Effect of the immunomodulant ximedone on the pharmacokinetics of isonicotinic acid hydrazide in the human organism

The pharmacokinetics of isonicotinic acid hydrazide upon joint administration with the immunomodulant ximedone has been investigated. Ximedone influences the genetically determined parameters of the isonicotinic acid hydrazide pharmacokinetics. The dose-dependent and temporal schedules of ximedone administration in humans are established, which favor the induction of acetylation processes in patients. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 3–6, March, 2006.     

Studies on the effect of penicillin, streptomycin and isonicotinic acid hydrazide on small intestinal oligosaccharidase.

Studies have been done on the effect of Penicillin, Streptomycin and Isonicotinic Acid hydrazide on small intestinal oligosaccharidase and it was observed that the drug penicillin inhibited the enzyme lactase and sucrase by 62.7% and 34.7% respectively, whereas I.N.H. inhibited the enzyme sucrase and maltase by 57.1% and 56.14% respectively. Streptomycin did not show any inhibitory effect on those enzymes. Lactose tolerance test showed impairment of lactose absorption in case of penicillin. Fasting serum sugar level was diminished both in penicillin and streptomycin and the absorption capacity was increased after oral administration of streptomycin.     

Effect of molybdenum and copper on key enzymes of rat kidney with special reference to physiological antagonism

Enzymological data on alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, cholinesterase and lipase obtained in the kidney of rats, fed on molybdenum (Mo) and copper (Cu), are reported. Antagonistic or synergistic behaviour has been determined by feeding the rats simultaneously on these two metals. Molybdenum inhibited all other enzymes except acid phosphatase and lipase. Complete inhibition of alkaline phosphatase was recorded after copper treatment. The combined treatment with molybdenum and copper exhibited reversible enzyme changes, however, cholinesterase activity remained inhibited.     

Integrative assessment of the developmental pharmacology and developmental toxicology, with special reference to the brain]

Increasing numbers of neurotoxins or therapeutic agents that have specific target cells or receptors can be used to assess the developmental correlation between the structure and function of various organs including the brain. Patients with chronic diseases are now able to maintain their social activities but still must be medicated for a long period of their life. This might increase the potential hazard of prenatal drug exposure in the progeny. Functional teratology is quite a new concept in neuroscience. Recent observations of our laboratory and those of others suggest that the sensitive period for functional teratology might encompass the whole stage of fetal life in animals and humans. The shortage of precise information on the developmental integration of the structure and function of the neurons with different properties is a problem to be solved for the further progress of developmental pharmacology and toxicology. Single exposures to drugs at a different stage during the gestational period of rats or mice might provide more useful information on the relationship between the lesioned area and related functional disorders manifested postnatally. This paper reviews recent advances in developmental neuropharmacology and functional neuroteratology including beneficial points of the short-term exposures to drugs.     

Cardiovascular pharmacology of quazodine (MJ-1988), with particular reference to effects on myocardial blood flow and metabolic heat production

1. The effects of intravenous infusions of quazodine (6,7-dimethoxy-4-ethylquinazoline; MJ-1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone.2. Quazodine (0.25 and 0.5 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end-diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.3. In a dose of (1.0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias.4. Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the beta-adrenoceptor blocking agent alprenolol in a dose (1.0 mg/kg) which abolished the effects of isoprenaline.5. In all doses, quazodine markedly increased local blood flow (by 70-540%) around an implanted myocardial heated thermocouple recorder. ;Corrected temperature', an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.