Yoshihide Fuse

Activation of inward current associated with M-potassium current inhibition in m1-muscarinic receptor-transformed NG108-15 cells by KST-5452, a novel cognition enhancer

The electrophysiological effects of KST-5452 [3-(m-phenoxybenzylidene)-quinuclidine], an M1 muscarinic acetylcholine receptor (muscarinic AChR) binding compound, were studied in NG108-15 neuroblastoma x glioma hybrid cells transfected with m1 muscarinic AChR cDNA. Application of KST-5452 to m1-transformed NGPM1-27 cells elicited a sustained inward current associated with decreased conductance and reduced M-current relaxations at a holding potential of -20 mV. The KST-5452-induced responses were blocked by pirenzepine, suggesting that KST-5452 acts as a potent excitant via M1 muscarinic AChRs in brain neurons.

Desalination and crystallization processes of lisinopril

An industrially advantageous method to separate Lisinopril and salts, formed by hydrolysis of Lisinopril ester with a base and subsequent neutralization with an acid, using a practical combination of base/acid, was investigated. This is an alternative to ion exchange treatment. In one method of crystallizing Lisinopril alone from the above neutralization mixture, while retaining a large amount of the salts dissolved therein, the presence of the inorganic salts had an adverse effect on crystallization of Lisinopril. In another method, by removing the salts in advance from the neutralization mixture by crystallization and filtration and then crystallizing Lisinopril, the inorganic salts were crystallized and removed, with little or no precipitation of Lisinopril, from a supersaturated solution of Lisinopril and then Lisinopril was crystallized. However, in production on an industrial scale which requires a long period of operation, this method involves a risk where the supersaturation is broken and the precipitation of Lisinopril occurs during the operation for removal of the salts. The above risk was overcome by introducing a protonation/deprotonation stage which controls the dissolution/precipitation of Lisinopril, and high quality Lisinopril dihydrate was effectively obtained.