Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-08-15
2000-01-25
Jarvis, William R. A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142312, 5142375, 5142275, 514319, A01N 4340, A61K 31445
Patent
active
060179295
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a cholinesterase activator, and more particularly to a cholinesterase activator which selectively enhances peripheral cholinesterase activities and is high in safety.
BACKGROUND ART
Cholinesterase is an enzyme that is widely distributed in a living body and hydrolyzes choline esters such as acetylcholine.
As the cholinesterase, there have heretofore been known two kinds of cholinesterase, i.e., specific (true) cholinesterase that exists in a brain, nervous tissue such as an autonomic nerve and a neuromuscules junction, an erythrocyte membrane, and the like, and nonspecific (pseudo) cholinesterase that exists in a serum, the pancreas and the like.
These kinds of cholinesterase are inhibited not only by cholinesterase inhibitors such as neostigmine but also by various medicines, in particular, carcinostatics, organic phosphorus agents and the like. The reduction in cholinesterase activities is considered to form the main cause that the side effects of various medicines are manifested. It is further known that cholinesterase activities are reduced even by hepatopathy.
For example, irinotecan hydrochloride, which is in use as a carcinostatic, is recognized to manifest grave diarrhea as a side effect. The diarrhea is manifested on the basis of a cholinesterase-inhibiting action due to administration of irinotecan hydrochloride.
Besides, 1,2,3,4-tetrahydro-9-acridinamine (hereinafter referred to as "THA") of a cholinesterase inhibitor, which has been used as a remedy for an Alzheimer's disease in recent years, inhibits not only central cholinesterase but also peripheral cholinesterase and is hence recognized to manifest side effects such as sialorrhea, nausea, diarrhea sweating and hepatopathy.
On the other hand, when the central cholinesterase is activated, the amount of acetylcholine in a brain is decreased, so that the diseased condition of a patient suffering from a Parkinson disease, senile dementia or the like is considered to be worsened.
Accordingly, it is necessary to administer an agent, which can selectively activate the peripheral cholinesterase, for the side effects of various medicines manifested on the basis of their cholinesterase-inhibiting action. However, any agent which can selectively activate central or peripheral cholinesterase has not been yet present, and there is hence a demand for development of a novel cholinesterase activator having such a selectively activating action.
The present inventors have carried out an extensive investigation with a view toward solving the above problem. As a result, it has been surprisingly found that a compound represented by the general formula (I) has a strongly activating action on cholinesterase, and such a activating action selectively works on peripheral cholinesterase, thus leading to completion of the present invention.
DISCLOSURE OF THE INVENTION
The present invention provides a cholinesterase activator comprising, as an active ingredient, a compound represented by the following general formula (I): ##STR2## wherein A means a group represented by the following general formula ##STR3## in which R.sup.1 and R.sup.2 are identical with or different from each other and denote individually a hydrogen atom, alkyl group, alkoxyl group, nitro group, amino group or halogen atom, R.sup.3 means a hydrogen atom or a hydroxyl group, B denotes a group represented by the following formula ##STR4## in which R.sup.4 denotes a hydrogen atom, formyl group, cyano group, dialkoxymethyl group, carboxyl group, alkoxycarbonyl group or hydroxymethyl group, X means a methylene group, ethylene group, oxygen atom, sulfur atom, sulfinyl group, sulfonyl group or --CH.sub.2 --S--, and Y represents a methylene group, ethylene group, --CH.sub.2 --S--, sulfur atom, sulfinyl group or sulfonyl group, and m stands for an integer of 0-5.
The present invention also provides an agent for preventing and treating a disease manifested on the basis of the reduction of cholinesterase activities, which comprises, as an active ingredient,
REFERENCES:
patent: 5120843 (1992-06-01), McCall et al.
Scopes et al., "New k-Receptor Agonists Based upon a 2-[(Alkylamino)methyl]piperidine Nucleus", J. Med. Chem 35 (No. 3), pp. 490-451, 1992.
Kobayashi Naomi
Mori Tadashi
Nakata Naoki
Tanaka Yoshiaki
Yamaguchi Itaru
Jarvis William R. A.
Jones Dwayne C.
Zeria Pharmaceutical Co. Ltd.
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