RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist.

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.

The medical and epidemiologic effects on workers of the levels of airborne Thermoactinomyces Spp. spores present in Australian raw sugar mills.

The objectives of the study were to determine whether there was a significant risk of members of the work force of raw sugar mills developing bagassosis. Airborne Thermoactinomyces sacchari spores were measured to determine whether they were sufficient to cause acute bagassosis, and whether there was any evidence of previous exposure to sufficient airborne T. sacchari spores to cause the development of chronic bagassosis in any of the work force. Monitoring of total airborne bacteria spore concentrations was undertaken in and around two cane sugar mills before, during, and after the 1992 cane processing season. Viable airborne bacteria counts were also obtained to confirm the presence of Thermoactinomyces sacchari. Area or zone samples at various sites around the mills and personal breathing zone samples from selected workers were obtained. The results showed that the total airborne bacteria spore count was lower than similar counts reported in other industries, such as cotton milling and wood chip handling, during normal operations. It was also found that the airborne counts during specific activities that generated higher than usual airborne spore levels were lower than expected from literature reports of handling similar material. Complementary medical examination of the entire full-time work forces of the two mills was carried out on a number of occasions during 1992. The medical data showed that no cases of acute bagassosis were detected, and that there was no evidence of the development of chronic bagassosis in any members of the work forces of either mill. Therefore, there is no significant risk of workers in the Australian sugar industry developing bagassosis.

Evidence for nitrogen catabolite repression during citric acid production by Aspergillus niger under phosphate-limited growth conditions.

Experiments performed in batch fermentation under phosphate-limited growth conditions showed that the citric acid yield was inversely related to the excess nitrogen concentration in the medium. Results from chemostat culture confirmed a negative relationship between the citric acid yield and both the specific growth rate and the nitrogen consumption rate. This is evidence for nitrogen catabolite repression. A fed-batch fermentation performed under dual phosphate/nitrogen limitation produced results very similar to those from a culture limited by nitrogen alone. There is no advantage in maintaining an excess of phosphate during citric acid production and the process will therefore be more economic when operated under dual limitation conditions.

Application of fed-batch culture to citric acid production by Aspergillus niger: The effects of dilution rate and dissolved oxygen tension.

Studies in conventional batch culture confirmed that the maximum citric acid production rate occurred prior to exhaustion of the growth-limiting nutrient, i.e., when the growth rate was nonzero. The effects of dilution rate and the culture dissolved oxygen tension (DOT) were studied in chemostat culture. Maximum citric acid yield and production rate were observed at low dilution rate (0.017 h(-1)) and high DOT value (90% of saturation). These findings were applied to a nitrogen-limited fed batch culture, and allowed a productivity increase of 100% when compared with conventional batch culture.