Tiapride HCl (Tiapridal), a benzamide derivative and an atypical neuroleptic agent, is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. Tiapride is a dopamine D2 and D3 receptor antagonist. It is more selective than other neuroleptic drugs such as haloperidol and risperidone, which not only target four of the five known dopamine receptor subtypes (D1-4), but also block serotonin (5-HT2A, 2C), α1- and α2-adrenergic, and histamine H1 receptors.

Physicochemical Properties

Molecular Formula	C15H25CLN2O4S
Molecular Weight	328.4271
Exact Mass	364.122
CAS #	51012-33-0
Related CAS #	Tiapride;51012-32-9
PubChem CID	5467
Appearance	White to off-white solid powder
Density	1.15 g/cm3
Boiling Point	498.1ºC at 760 mmHg
Melting Point	124 °C
Flash Point	255.1ºC
LogP	3.627
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	22
Complexity	443
Defined Atom Stereocenter Count	0
SMILES	S(C([H])([H])[H])(C1C([H])=C([H])C(=C(C=1[H])C(N([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)OC([H])([H])[H])(=O)=O
InChi Key	OTFDPNXIVHBTKW-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H24N2O4S.ClH/c1-5-17(6-2)10-9-16-15(18)13-11-12(22(4,19)20)7-8-14(13)21-3;/h7-8,11H,5-6,9-10H2,1-4H3,(H,16,18);1H
Chemical Name	N-(2-(Diethylamino)ethyl)-2-methoxy-5-(methylsulphonyl)benzamide monohydrochloride
Synonyms	Trade names in Italy (Italprid, Sereprile), Japan (Tialaread, Tiaryl, Tiaprim, Tiaprizal), Chile (Sereprid), Germany (Tiaprid, Tiapridex), and China (Tiapride); Tiapride HCl, Tiapride Hydrochloride;
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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

ADME/Pharmacokinetics	Absorption, Distribution and Excretion The bioavailability of tiapride is approximately 75 percent. It has a Tmax is 0.4-1.5 hours and Tss is 24-48 hours with 3 time daily dosing. Benzamide and its derivatives are highly water-soluble but known to cross the blood-brain barrier, necessitating carrier-mediated transport. Urine (70% as unchanged tiapride) Tiapride distributes rapidly and exhibits virtually no binding to plasma proteins, giving it a relatively high volume of distribution 16.6 l/h. Metabolism / Metabolites Tiapride is minimally metabolized in humans, 70 % of the drug is eliminated in unchanged form in the urine within 24 hours. Only low concentration of N-desethyl tiapride and tiapride N-oxide and no phase II metabolites were detected. Biological Half-Life 2.9–3.6 hours
Toxicity/Toxicokinetics	Protein Binding Negligible
References	Nagamine T. Severe Hypoglycemia Associated with Tiapride in an Elderly Patient with Diabetes and Psychosis. Innov Clin Neurosci. 2017 Feb 1;14(1-2):12-13. eCollection 2017 Jan-Feb.
Additional Infomation	N-[2-(diethylamino)ethyl]-2-methoxy-5-methylsulfonylbenzamide is a member of benzamides. Tiapride is a selective D2 and D3 dopamine receptor blocker in the brain. A benzamide derivative that is used as a dopamine antagonist. See also: Tiapride Hydrochloride (annotation moved to). Drug Indication Tiapride is indicated for the treatment of a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. Mechanism of Action Tiapride is a selective dopamine D2 and D3 receptor antagonist, offering an advantage over other neuroleptic drugs, such as haloperidol and risperidone, which bind a range of targets including four of the five known dopamine receptor subtypes (D1-4), serotonin (5-HT2A, 2C), α1- and α2-adrenergic, and histamine H1 receptors. Compared to these drugs, tiapride has a relatively moderate affinity for its target receptors, displacing 50 percent of 3H-raclopride binding at a concentration of 320 nM at D2 receptors and a concentration of 180 nM at D3 receptors. Pharmacodynamics Tiapride has a high degree of regional selectivity for limbic areas. One study found that tiapride shows over three times as much affinity for limbic areas than striatal areas as opposed to the near equal selectivity for limbic and striatal regions shown by haloperidol. Another study in rats found tiapride's affinity for the septum, a limbic region, to be over thirty times as high as for the striatum. Efficacy at the D2 receptor is moderate, with 80 percent of receptors occupied even in the presence of excess tiapride concentrations.

Solubility Data

Solubility (In Vitro)

H2O : ≥ 200 mg/mL (~548.11 mM) DMSO : ~31.25 mg/mL (~85.64 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.62 mg/mL (1.70 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 6.2 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: ≥ 0.62 mg/mL (1.70 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 6.2 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: ≥ 0.62 mg/mL (1.70 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 6.2 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (274.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0448 mL	15.2239 mL	30.4479 mL
	5 mM	0.6090 mL	3.0448 mL	6.0896 mL
	10 mM	0.3045 mL	1.5224 mL	3.0448 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.