P2‐318: Tdcs stimulation alongside picture training improves naming scores in anomic dementia patients

for cognitive improvement. Targeting the less conserved allosteric site provides selectivity and the advantage of obtaining pharmacological agents with lesser side effects. SUVN-I1312004 is being actively pursued as a potential for cognitive improvement with lesser side effects. Methods:SUVN-I1312004 was assessed by reporter gene assay against various muscarinic receptor sub-types M2, M3 and M5. SUVN-I1312004 was assessed for agonist activity up to the maximal tested concentration of 10mM. SUVNI1312004 was also assessed in radio ligand binding study upto 10mM. Pharmacokinetic profile and brain penetration was studied in male Wistar rats. Efficacy of SUVN-I1312004 was assessed in various cognitive tasks such as object recognition task (ORT) and fear conditioning assay. Safety of SUVN-I1312004 was also evaluated. Results: The selectivity panel reveals an affinity forM1 receptor in comparison toM2-M5 receptor. In the functional reporter gene assay at human M1 muscarinic receptor, SUVN-I1312004 shifted acetylcholine dose response towards left with a 57 fold shift of acetylcholine potency at 10mM with an EC50 (inflection point) of 337 nM, which proves that SUVN-I1312004 is a potent positive allosteric modulator. SUVN-I1312004 did not show any binding affinity up to the maximal tested concentration of 10mM towards muscarinic receptor subtypesM1, M2,M3 andM4. SUVN-I1312004 had favorable pharmacokinetic profile and adequate brain penetration in male Wistar rats. SUVN-I1312004 enhanced the discriminative index when administered alone and or in combination with donepezil in ORT. SUVN-I1312004 enhanced the duration of freezing in the fear conditioning test, memory deficit being induced by scopolamine. No potentiation in salivation was observed when coadministered with donepezil in the salivation assay. SUVNI132004 demonstrated a wide margin of safety in early toxicity studies. Conclusions: SUVN-I1312004 is a novel, potent, selective, orally bioavailable and efficacious M1-PAM that holds promise for the treatment of AD and dementia. SUVN-I1312004 is being further evaluated for various safety parameters.