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Functional connectivity was significantly reduced after TAK-071 at high doses and was enhanced with coadministration of donepezil under the eyes-closed condition. PK and safety profiles of TAK-071 were favorable, including those exceeding expected pharmacologically active doses based on preclinical data. When administered without donepezil TAK-071 was largely free of cholinergic adverse effects. Further clinical evaluation of TAK-071 is warranted. PK and safety profiles of TAK-071 were favorable, including those exceeding expected pharmacologically active d