Sabcomeline hydrochloride  (Synonyms: SB-202026 hydrochloride; Memric hydrochloride)

Sabcomeline (SB-202026; Memric) hydrochloride is a muscarinic receptor agonist capable of crossing the blood-brain barrier. Sabcomeline hydrochloride exhibits affinity for all hM1 to hM5 subtypes (pK_i=6.72-7.23), and shows near-full agonism at the hM3 receptor, inducing extracellular acidification. Sabcomeline hydrochloride alters the binding kinetics of dopamine D2 receptors through neural network regulation. Sabcomeline hydrochloride also causes minimal cardiovascular changes, effectively reverses spatial memory deficits in rodents and induces conditioned taste aversion. Sabcomeline hydrochloride is an important tool compound in studies of Alzheimer's disease and related neurodegenerative diseases^[1][2][3].

Compared with Carbamoylcholine (HY-B1208), Sabcomeline hydrochloride exhibits the lowest potency (≈20%) at the hM₁ and hM₅ subtypes; moderate potency at the hM₄ (≈38%) and hM₂ (≈57%) subtypes; and the highest partial agonist potency (≈70%) at the hM₃ subtype^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Sabcomeline hydrochloride (0.01-3 mg/kg; i.v.; 0.3 mg/kg; i.p.) exhibits dose-dependent, non-M₁-selective mACh receptor binding in mouse brain and heart with rapid dissociation (return to control levels by 3-4 hours post-0.3 mg/kg i.v. dose), and alters striatal dopamine D₂ receptor binding kinetics by decreasing [³H]NMSP k₃ by ~15% and increasing [³H]raclopride BP by ~20%^[2].
Sabcomeline hydrochloride (0.03-0.1 mg/kg; i.p.; single dose 15 minutes prior to testing) significantly reverses 20-s delay-induced T-maze choice accuracy deficits in male Hooded Lister rats, with cholinergic side effects appearing at higher doses of 0.3 mg/kg and above^[3].
Sabcomeline hydrochloride (0.3-1.0 mg/kg; i.p.; single dose 15 minutes after saccharin exposure) induces significant conditioned taste aversion in male Hooded Lister rats at a minimum effective dose of 0.3 mg/kg, with 60% inhibition of saccharin intake observed at 1.0 mg/kg^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

229.71

C₁₀H₁₆ClN₃O

159912-58-0

Solid

White to off-white

CO/N=C([C@@H]1C2CCN(CC2)C1)\C#N.Cl

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Wood M D, et al. Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry[J]. British journal of pharmacology, 1999, 126(7): 1620.

  [2]. Hosoi R, et al. Effect of sabcomeline on muscarinic and dopamine receptor binding in intact mouse brain. Ann Nucl Med. 2003;17(2):123-130.  [Content Brief]

  [3]. Hatcher JP, et al. Sabcomeline (SB-202026), a functionally selective M1 receptor partial agonist, reverses delay-induced deficits in the T-maze. Psychopharmacology (Berl). 1998;138(3-4):275-282.  [Content Brief]