(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3') quinuclidine (AF102B): a new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats.
(+-)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.
Fisher
A
A
Israel Institute for Biological Research, Ness-Ziona.
Brandeis
R
R
Pittel
Z
Z
Karton
I
I
Sapir
M
M
Dachir
S
S
Levy
A
A
Heldman
E
E
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002794:Choline / Q000494:pharmacology / Q000031:analogs & derivatives; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D008297:Male; D015394:Molecular Structure; D010277:Parasympathomimetics / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013876:Thiophenes
D001388:Aziridines; D010277:Parasympathomimetics; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013876:Thiophenes; C044894:ethylcholine aziridinium; C059240:cevimeline; D002794:Choline