Abstract
The emergence of a novel theory concerning the role of noradrenaline in the progression and the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases has provided a new impetus toward the discovery of novel compounds acting at alpha(2)-adrenoceptors. A series of substituted 1-(2, 3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl derivatives bearing an amide, urea, or imidazolidinone moiety was studied. Some members of this series of compounds proved to be potent alpha(2)-adrenoceptor antagonists with good selectivity versus alpha(1)-adrenergic and D(2)-dopamine receptors. Particular emphasis is given to compound 33g which displays potent alpha(2)-adrenoceptor binding affinity in vitro and central effects in vivo following oral administration.
MeSH terms
-
Adrenergic alpha-Agonists
-
Adrenergic alpha-Antagonists / chemical synthesis*
-
Adrenergic alpha-Antagonists / chemistry
-
Adrenergic alpha-Antagonists / metabolism
-
Adrenergic alpha-Antagonists / pharmacology
-
Animals
-
Cerebral Cortex / metabolism
-
Corpus Striatum / metabolism
-
Dioxanes / chemical synthesis*
-
Dioxanes / chemistry
-
Dioxanes / metabolism
-
Dioxanes / pharmacology
-
Guanabenz
-
Hypothermia / chemically induced
-
Hypothermia / drug therapy
-
Imidazoles / chemical synthesis*
-
Imidazoles / chemistry
-
Imidazoles / metabolism
-
Imidazoles / pharmacology
-
In Vitro Techniques
-
Male
-
Membranes
-
Mice
-
Neuroglia / metabolism
-
Rats
-
Receptors, Adrenergic, alpha-1 / drug effects
-
Receptors, Adrenergic, alpha-1 / metabolism
-
Receptors, Adrenergic, alpha-2 / drug effects*
-
Receptors, Dopamine D2 / drug effects
-
Receptors, Dopamine D2 / metabolism
-
Structure-Activity Relationship
Substances
-
1-(2-(1-(2,3-dihydrobenzo(1,4)dioxin-2-ylmethyl)piperidin-4-yl)ethyl)-3-(2,4,6-trimethoxyphenyl)imidazolidin-2-one
-
Adrenergic alpha-Agonists
-
Adrenergic alpha-Antagonists
-
Dioxanes
-
Imidazoles
-
Receptors, Adrenergic, alpha-1
-
Receptors, Adrenergic, alpha-2
-
Receptors, Dopamine D2
-
Guanabenz