Rhône-Poulenc

About: Rhône-Poulenc is a based out in . It is known for research contribution in the topics: Alkyl & Catalysis. The organization has 8909 authors who have published 8934 publications receiving 182241 citations. The organization is also known as: Rhone-Poulenc.

Purification, characterization, and molecular cloning of S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase from Methanobacterium ivanovii.

Abstract: An S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) activity has been identified in Methanobacterium ivanovii and was purified 4,500-fold to homogeneity with a 38% yield. The enzyme had an apparent molecular weight of 58,200 by gel filtration and consisted of two identical subunits of Mr 29,000, as estimated by gel electrophoresis under denaturing conditions. The Km value for uroporphyrinogen III was 52 nM. The enzyme catalyzed the two C-2 and C-7 methylation reactions converting uroporphyrinogen III into precorrin-2. Unlike Pseudomonas denitrificans SUMT, the only SUMT characterized to date (F. Blanche, L. Debussche, D. Thibaut, J. Crouzet and B. Cameron, J. Bacteriol. 171:4222-4231, 1989), M. ivanovii SUMT did not show substrate inhibition at uroporphyrinogen III concentrations of up to 20 microM. Oligonucleotide probes from limited peptide sequence information were used to clone the corresponding gene. The encoded polypeptide showed more than 40% strict homology with P. denitrificans SUMT. The M. ivanovii SUMT structural gene is likely to be, as is P. denitrificans cobA, involved in corrinoid synthesis.

The gastrin/cholecystokinin-B receptor antagonist L-365,260 reduces basal acid secretion and prevents gastrointestinal damage induced by aspirin, ethanol and cysteamine in the rat.

Abstract: L-365,260, a nonpeptide antagonist of gastrin/CCK-B receptors, was evaluated in receptor binding, antisecretory and gastrointestinal damage assays. L-365,260 binds potently and stereo-selectively to gastrin and CCK-B sites in guinea pig tissue. In contrast, L-365,260 binds to the isolated canine parietal cell gastrin receptor weakly, and without stereoselectivity. In the pylorus-ligated rat, low doses of L-365,260, given i.v., attenuated pentagastrin-stimulated acid secretion, whereas higher doses were required to inhibit both histamine-stimulated and basal acid secretion. In an aspirin-induced gastric damage model, L-365,260 was 2.4-fold less potent than the standard histamine H2 antagonist cimetidine in preventing gastric damage when given i.v., and was 8.3-fold less potent than cimetidine when given p.o. Moreover, the ED50 value for L-365,260, given i.v., in prevention of aspirin-induced gastric damage (11.5 mg/kg) agreed well with its ED50 value for inhibition of basal acid secretion (12.6 mg/kg). At doses as great as 100 mg/kg p.o., neither L-365,260 nor cimetidine had an effect on ethanol-induced gastric damage. L-365,260, although p.o. less bioavailable relative to cimetidine in the aspirin gastric damage model, was as potent as cimetidine in the prevention of cysteamine-induced duodenal ulcers in the rat. We conclude that the gastrin/CCK-B receptor antagonist L-365,260, at doses supramaximal for the inhibition of pentagastrin-stimulated secretory responses in vivo, inhibits gastrointestinal damage in models of peptic ulcer disease by an antisecretory mechanism of action.

A Comparison of the Pharmacokinetics and Tolerability of Riluzole after Repeat Dose Administration in Healthy Elderly and Young Volunteers

Abstract: The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender- and weight-matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender. The mean terminal elimination half-life (t1/2), however, was statistically significant between elderly and young subjects. Riluzole was well tolerated upon repeat dose administration. Headache was the most frequent adverse event reported, and there was no overt difference in the type, frequency, or severity of adverse events between elderly and young volunteers or between genders. In conclusion, these results indicate that no dosage adjustments of riluzole are required in the elderly.

Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside.

Abstract: 1 The effects of the selective inhibitors of cyclic AMP phosphodiesterase type IV (rolipram) and type III (siguazodan) and their interactions with isoprenaline and sodium nitroprusside have been studied in the human isolated bronchus. 2 On bronchi under resting tone rolipram was, in terms of potency (pD2 = 7.77 +/- 0.14, n = 8), very similar to isoprenaline (pD2 = 7.31 +/- 0.12, n = 12) and salbutamol (pD2 = 7.12 +/- 0.17, n = 10) and approximately 10 fold more potent than siguazodan (pD2 = 6.80 +/- 0.12, n = 6). In terms of efficacy (Emax, expressed as percentage of maximal effect induced by theophylline 3 mM), both rolipram and siguazodan were less efficient (Emax = 74 +/- 6.7%, n = 8 and 66 +/- 7.5%, n = 6, respectively) than isoprenaline (Emax = 98 +/- 0.4%, n = 12) and salbutamol (Emax = 83 +/- 2.4%, n = 10). 3 During precontraction induced by methacholine (3 x 10(-7) M) or acetylcholine (10(-3) M), concentration-response curves to rolipram and siguazodan were shifted to the right and maximal effects reduced. Rolipram was more potent than siguazodan and, in terms of efficacy, it was less active. 4. Rolipram 10(-8) and 10(-7) M but not siguazodan potentiated the effects of isoprenaline as shown by the shift to the left of the concentration-response curve to isoprenaline. Sodium nitroprusside-induced relaxation was not modified by either drug. 5. These results show that rolipram is a potent relaxant of the human isolated bronchus, potentiating the effects of beta-adrenoceptor stimulation and suggest that, as previously demonstrated in other species(guinea-pig, cow) (Tomkinson et al., 1993), there may be a connection between the beta2-adrenoceptor subtype, which predominate in human airway smooth muscle, and the cyclic AMP phosphodiesterase type IV.