159912-53-5Relevant articles and documents
MONO AND COMBINATION THERAPY WITH M1/M4 MUSCARINIC AGONIST (SABCOMELINE) FOR TREATMENT OF PRODROMAL SYNDROME
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Page/Page column 12, (2010/11/29)
The invention relates to the use of a functional muscarinic M1/M4 agonist or a pharmaceutically acceptable salt thereof to treat prodromal syndrome and in the manufacture of a medicament for the treatment of prodromal syndrome, and to a method of treatment of prodromal syndrome using a functional muscarinic M1/M4 agonist or a pharmaceutically acceptable salt thereof. It also relates to the use of a pharmaceutical composition comprising a functional muscarinic M1/M4 agonist or a pharmaceutically acceptable salt thereof, and at least one cholinergic agent and/or at least one non-cholinergic agent for the treatment of prodromal syndrome, and to a method of treatment of prodromal syndrome by administration of a such a pharmaceutical composition.
MONO AND COMBINATION THERAPY WITH A M1/M4 MUSCARINIC AGONIST (SABCOMELINE) FOR TREATMENT OF COGNITIVE DISORDERS IN SCHIZOPHRENIA
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Page/Page column 30, (2008/06/13)
The invention relates to the use of a functional muscarinic M1/M4 receptor agonist such as the functional muscarinic M1/M4 receptor agonist or a pharmaceutically acceptable salt thereof, in particular sabcomeline or a pharmaceutically acceptable salt thereof in for the treatment of cognitive impairment in schizophrenia and to combination therapies for the treatment of cognitive impairment in schizophrenia which the functional muscarinic M1/M4 receptor agonist or a pharmaceutically acceptable salt thereof, in particular sabcomeline or a pharmaceutically acceptable salt thereof and at least one other neuroprotective agent and/or neuroleptic and/or atypical antipsyhcotic agent are administered adjunctively or simultaneously. The invention provides methods of treatment of cognitive impairment in schizophrenia utilising such therapies and such adjunctive or simultaneous therapeutic combination therapies, therapeutic combinations for use therein and pharmaceutical compositions comprising them.
Design of [R-(Z)]-(+)-α-(methoxyimino)-1-azabicyclo[2.2.2]octane-3- acetonitrile (SB 202026), a functionally selective azabicyclic muscarinic M1 agonist incorporating the N-methoxy imidoyl nitrile group as a novel ester bioisostere
Bromidge, Steven M.,Brown, Frank,Cassidy, Frederick,Clark, Michael S. G.,Dabbs, Steven,Hadley, Michael S.,Hawkins, Julie,Loudon, Julia M.,Naylor, Christopher B.,Orlek, Barry S.,Riley, Graham J.
, p. 4265 - 4280 (2007/10/03)
Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisotere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile (R)-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)- (Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.
