Spiradoline (U-62066), an arylacetamide, is a selective kappa opioid receptor (KOR) agonist/activator with a Ki of 8.6 nM in guinea pigs. The Kis of Spiradoline for μ and δ receptors are 252 nM and 9400 nM respectively. Spiradoline has potent diuretic, analgesic, antiarrhythmic, antitussive, neuro-protection effects and readily crosses the BBB (blood-brain barrier).

Physicochemical Properties

Molecular Formula	C22H30CL2N2O2
Molecular Weight	425.39
Exact Mass	424.168
CAS #	87151-85-7
Related CAS #	Spiradoline mesylate;87173-97-5
PubChem CID	55652
Appearance	Typically exists as solid at room temperature
LogP	4.498
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	557
Defined Atom Stereocenter Count	3
SMILES	N([C@H]1CC[C@]2(OCCC2)C[C@@H]1N1CCCC1)(C)C(=O)CC1C=CC(Cl)=C(Cl)C=1
InChi Key	NYKCGQQJNVPOLU-ONTIZHBOSA-N
InChi Code	InChI=1S/C22H30Cl2N2O2/c1-25(21(27)14-16-5-6-17(23)18(24)13-16)19-7-9-22(8-4-12-28-22)15-20(19)26-10-2-3-11-26/h5-6,13,19-20H,2-4,7-12,14-15H2,1H3/t19-,20-,22-/m0/s1
Chemical Name	2-(3,4-dichlorophenyl)-N-methyl-N-[(5R,7S,8S)-7-pyrrolidin-1-yl-1-oxaspiro[4.5]decan-8-yl]acetamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Ki: 8.6 nM (κ-opioid receptor in guinea pig), 252 nM (μ-receptor) and 9400 nM (δ-receptor)[2]
ln Vitro	Employing the patch-clamp technique on isolated rat heart myocytes, it was found that spirol (15–500 μM) inhibits potassium currents and sodium channels in cardiac tissue to create its antiarrhythmic activity. At higher concentrations, it also blocks potassium channels. Consequently, spiradoline decreases the sustained plateau potassium amplitude, increases the decay rate of the transient outward potassium current, and decreases the peak sodium current[2].
ln Vivo	In non-stressed adults, Spiradoline (U-62066; 0.1-0.4 mg/kg; subcutaneous injection; once; Sprague-Dawley rats) treatment dose-dependently decreases social behaviors, resulting in social avoidance at the highest dose tested. However, in younger animals, Spiradoline's socially suppressive effect is less pronounced. The Spiradoline's socially suppressive effects are attenuated in stressed animals at all ages, with juveniles and adolescents responding to specific dosages of U-62066 with greater social preference[1].
Animal Protocol	Animal/Disease Models: Juvenile, adolescent and adult SD (Sprague-Dawley) male and female rats exposed to repeated restraint[1] Doses: 0.1 mg/kg, 0.2 mg/kg, 0.3 mg/kg, and 0.4 mg/kg Route of Administration: subcutaneous (sc) injection; once Experimental Results: Dose -dependently decreased social behaviors in non-stressed adults, producing social avoidance at the highest dose tested.
References	[1]. Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats. Neurobiol Stress. 2018 Sep 11;9:124-132. [2]. M-L G Wadenberg. A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. CNS Drug Rev. Summer 2003;9(2):187-98.
Additional Infomation	Spiradoline has been investigated for the basic science of Bipolar Depression.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (117.54 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3508 mL	11.7539 mL	23.5078 mL
	5 mM	0.4702 mL	2.3508 mL	4.7016 mL
	10 mM	0.2351 mL	1.1754 mL	2.3508 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.