Various neurodegenerative diseases and psychiatric disorders are marked by alterations in brain cholinergic function and cognitive deficits.
Efforts to alleviate such deficits have been limited by a lack of selective M(1) muscarinic agonists. 5-(3-Ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A) is a partial agonist at M(1) muscarinic receptors with limited activity at other muscarinic receptor subtypes.
The present studies investigated the effects of CDD-0102A on working memory and strategy shifting in rats. CDD-0102A administered intraperitoneally 30 min before testing at 0.1, 0.3, and 1 mg/kg significantly enhanced delayed spontaneous alternation performance in a four-arm cross maze, suggesting improvement in working memory.
In separate experiments, CDD-0102A had potent enhancing effects on learning and switching between a place and visual cue discrimination.
Treatment with CDD-0102A did not affect acquisition of either a place or visual cue discrimination.
In contrast, CDD-0102A at 0.03 and 0.1 mg/kg significantly enhanced a shift between a place and visual cue discrimination.
Analysis of the errors in the shift to the place or shift to the visual cue strategy revealed that in both cases CDD-0102A significantly increased the ability to initially inhibit a previously relevant strategy and maintain a new, relevant strategy once selected.
In anesthetized rats, the minimum dose required to induce salivation was approximately 0.3 mg/kg i.p. Salivation increased with dose, and the estimated ED(50) was 2.0 mg/kg. The data suggest that CDD-0102A has unique memory and cognitive enhancing properties that might be useful in the treatment of neurological disorders at doses that do not produce adverse effects such as salivation.
2012-02-15
Eng.
The Journal of pharmacology and experimental therapeutics
Department of Psychology, Laboratory of Integrative Neuroscience, University of Illinois at Chicago, Chicago, Illinois, USA.
J Pharmacol Exp Ther. 2012 Mar;340(3):588-94
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