This article is a summary of the molecular patho-pharmacological studies continuously investigated for more than 30 years in Toyama Medical & Pharmaceutical University. The aim of this study was to develop the motivation and the strategy for the original drug-design by targeting the pharmacological mechanism of receptor modified by the pathological state in the animal models for the diseases, followed by searching the pathoreceptor-sensitive drugs as a probe of new medicines. The drug activity consists of two factors, affinity and intrinsic activity to the receptor, depend on their chemical structures of supporting moiety and radical moiety, respectively. The former can be discovered from the natural products, composing Japanese traditional Sine-medicines, and the latter can be modified by chemical synthesis. By using this strategy, several new findings, a large number of new compounds and/or new pharmacological activity, were obtained as follows. I. On the molecular pharmacology of nicotinic ACh receptor. II. On the development of new drugs affecting on smooth muscle. III. On the pathopharmacological investigation with a model of diabetic mice. IV. On the applied pharmacology of Japanese traditional Sine-medicines.
