CDD-0102

CDD-0102, the hydrochloride salt of 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine (designated CDD-0102A in its salt form), is a functionally selective partial agonist at the M1 subtype of the muscarinic acetylcholine receptor developed at the University of Toledo College of Pharmacy under the direction of W.S. Messer Jr. as a candidate therapeutic for Alzheimer's disease and related cognitive disorders. The compound occupies the orthosteric acetylcholine-binding site of the M1 receptor with partial agonist intrinsic activity sufficient to activate phospholipase C-coupled signaling, stimulate non-amyloidogenic processing of amyloid precursor protein (APP) through alpha-secretase, and enhance cognitive function in rodent models of cholinergic deficit, while exhibiting minimal functional activity at M2, M4, and M5 muscarinic subtypes and only weak activity at M3 receptors. This functional selectivity profile distinguishes CDD-0102 from the first-generation M1-preferring muscarinic agonists (xanomeline, sabcomeline, talsaclidine, cevimeline) that produced dose-limiting cholinergic adverse events (salivation, gastrointestinal disturbance, diaphoresis) attributable to activation of peripheral M2 and M3 receptors, a limitation that terminated or constrained the clinical development of each of those compounds in the Alzheimer's indication. The pharmacological characterization of CDD-0102 encompasses M1-selective receptor binding, stimulation of soluble APP-alpha (sAPPalpha) secretion from Chinese hamster ovary cells stably expressing human M1 receptors, neuroprotective activity in cell culture, brain penetration following systemic administration in rodents, oral bioavailability, and a favorable acute toxicity profile. In behavioral pharmacology, CDD-0102A administered intraperitoneally at doses of 0.03 to 1.0 mg/kg enhances delayed spontaneous alternation in a four-arm cross maze (a measure of spatial working memory) and facilitates strategy switching between place and visual-cue discriminations (a measure of cognitive flexibility), with both effects following a dose-dependent profile and occurring at doses below the threshold for salivation (approximately 0.3 mg/kg intraperitoneal for the minimum effective salivation dose, with an estimated ED50 for salivation of 2.0 mg/kg). More recent preclinical work has extended the pharmacological profile to autism spectrum disorder models, demonstrating that CDD-0102A attenuates stereotyped motor behaviors (self-grooming, digging) and modulates glutamate efflux in dorsolateral striatum of the BTBR T+ Itpr3tf/J mouse, a model of autism-relevant repetitive behavior and social deficit. The compound advanced through preclinical development with support from the National Center for Advancing Translational Sciences (NCATS) Bridging Interventional Development Gaps (BrIDGs) program, which funded the IND-enabling studies including synthetic scale-up, formulation, pharmacokinetics, and toxicology. An Investigational New Drug (IND) application was filed with the United States Food and Drug Administration, and Phase 1 clinical testing was initiated. Published results from Phase 1 clinical evaluation have not appeared in the peer-reviewed literature as of the most recent monograph revision. The compound is not registered as a marketed medicine in any jurisdiction. This monograph reviews the chemistry, synthesis, and structural class of CDD-0102; the M1 muscarinic receptor pharmacology in molecular and functional detail; the preclinical evidence base across Alzheimer's disease, cognitive flexibility, and autism-relevant endpoints; the available pharmacokinetic characterization; sourcing and quality verification considerations for research applications; reconstitution and handling; stack-interaction considerations; the adverse-event and safety profile; and a comparative assessment of five M1 muscarinic receptor agonist candidates (xanomeline, sabcomeline, talsaclidine, AF267B, cevimeline) against CDD-0102 on five competency standards (novelty, effect size, promising potential, side-effect profile, and overall validation).