Raclopride (formerly FLA 870) is a novel, potent and selective dopamine D2/D3 receptor antagonist, which binds to D2 and D3 receptors with dissociation constants (Kis) of 1.8 nM and 3.5 nM, respectively, but has a very low affinity for D1 and D4 receptors with Kis of 18000 nM and 2400 nM, respectively. Raclopride's selectiveness for cerebral D2 receptors is indicated by its Ki-values, which are 1.8, 3.5, 2400, and 18000 nM for D2, D3, D4, and D1 receptors, respectively. It can be radiolabelled with radioisotopes, such as 3H or 11C, and used as a tracer for positron emission tomography (PET) and in vitro imaging (autoradiography). The non-invasive evaluation of the binding capacity of the cerebral D2 dopamine receptor is made possible by images acquired by cerebral PET scanning (e.g., PET/CT or PET/MRI), which can be helpful in the diagnosis of movement disorders.

Physicochemical Properties

Molecular Formula	C₁₅H₂₀CL₂N₂O₃
Molecular Weight	347.24
Exact Mass	346.085
CAS #	84225-95-6
Related CAS #	Raclopride-d5 hydrochloride; 1217623-85-2; Raclopride tartrate; 98185-20-7
PubChem CID	3033769
Appearance	White to yellow solid powder
Density	1.288g/cm3
Boiling Point	420.3ºC at 760 mmHg
Melting Point	54 °C
Flash Point	208ºC
Index of Refraction	1.563
LogP	3.25
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	22
Complexity	386
Defined Atom Stereocenter Count	1
SMILES	CCN1CCC[C@H]1CNC(=O)C2=C(C(=CC(=C2OC)Cl)Cl)O
InChi Key	WAOQONBSWFLFPE-VIFPVBQESA-N
InChi Code	InChI=1S/C15H20Cl2N2O3/c1-3-19-6-4-5-9(19)8-18-15(21)12-13(20)10(16)7-11(17)14(12)22-2/h7,9,20H,3-6,8H2,1-2H3,(H,18,21)/t9-/m0/s1
Chemical Name	3,5-dichloro-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-6-methoxybenzamide
Synonyms	FLA 870; FLA-870; RACLOPRIDE; 84225-95-6; (S)-3,5-dichloro-N-((1-ethylpyrrolidin-2-yl)methyl)-2-hydroxy-6-methoxybenzamide; 3,5-dichloro-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-6-methoxybenzamide; CHEMBL8809; 430K3SOZ7G; DTXSID9045687; NCGC00025303-03; FLA870; Raclopride
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	D2 Receptor ( Ki = 1.8 nM ); D3 Receptor ( Ki = 3.5 nM ); D4 Receptor ( Ki = 2400 nM ); D1 Receptor ( Ki = 18000 nM )
ln Vivo	Raclopride (0.1, 0.3, or 0.6 mg/kg; IP; 30 min; albino male mice; OF1 strain) dramatically shortens the amount of time that the mice spend engaging in aggressive behavior[2]. Raclopride is a substituted benzamide with high selectivity as an antagonist of central dopaminergic D2 receptors and potential antipsychotic effects. In comparison with a classic DA receptor blocking agent like haloperidol, raclopride displays an atypical profile in preclinical tests for extrapyramidal side effects. Antiaggressive properties of raclopride on agonistic behavior have not yet been fully explored. In this work the effects of raclopride (0.1, 0.3, or 0.6 mg/kg) on aggressive and motor behaviors in male mice were studied. Aggression tests were performed 30 min after injections. Encounters were videotaped and behavior was evaluated, measuring the time spent in 11 broad categories of behavior. The results show a clear antiaggressive effect of raclopride, with very little motor impairment and some increase in exploratory behavior. This behavioral profile is very similar to the one observed with other atypical neuroleptics and differs somewhat from that found in the classic compounds.[2]
Animal Protocol	Albino male mice of the OF1 strain 0.1, 0.3, or 0.6 mg/kg i.p.
References	[1]. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):264-70. [2]. Behavioral profile of raclopride in agonistic encounters between male mice. Pharmacol Biochem Behav. 1994;47(3):753-756.
Additional Infomation	3,5-dichloro-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2-hydroxy-6-methoxybenzamide is a member of salicylamides. Raclopride has been used in trials studying Parkinson Disease. A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist. Dopamine receptors are the primary targets in the treatment of schizophrenia, Parkinson's disease, and Huntington's chorea, and are discussed in this review by Philip Seeman and Hubert Van Tol. Improved therapy may be obtained by drugs that selectively target a particular subtype of dopamine receptor. Most antipsychotic drugs block D2 receptors in direct correlation to clinical potency, except clozapine, which prefers D4 receptors. D1 and D2 receptors can enhance each other's actions, possibly through subunits of the G proteins. In schizophrenia, the D2 and D3 receptor density is elevated by 10%, while the D4 receptor density is elevated by 600%. Therefore, D4 receptors may be a target for future antipsychotic drugs. While antipsychotics originally helped to discover dopamine receptors, the five cloned dopamine receptors are now facilitating the discovery of selective antipsychotic and antiparkinson drugs. Antipsychotic Agents Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.) Dopamine Antagonists Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Solubility Data

Solubility (In Vitro)

DMSO: 69~100 mg/mL (198.7~288 mM) Ethanol: ~69 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.20 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 (7.20 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 (7.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 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	2.8799 mL	14.3993 mL	28.7985 mL
	5 mM	0.5760 mL	2.8799 mL	5.7597 mL
	10 mM	0.2880 mL	1.4399 mL	2.8799 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.