SERTINDOLE Chemical Properties

Melting point:

95-100°C

Boiling point:

592.1±50.0 °C(Predicted)

Density 

1.36

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO: >10mg/mL

form 

solid

pka

14.53±0.20(Predicted)

color 

off-white

Merck 

14,8466

InChI

InChI=1S/C24H26ClFN4O/c25-18-1-6-23-21(15-18)22(16-30(23)20-4-2-19(26)3-5-20)17-7-10-28(11-8-17)13-14-29-12-9-27-24(29)31/h1-6,15-17H,7-14H2,(H,27,31)

InChIKey

GZKLJWGUPQBVJQ-UHFFFAOYSA-N

SMILES

C1(=O)N(CCN2CCC(C3C4=C(N(C5=CC=C(F)C=C5)C=3)C=CC(Cl)=C4)CC2)CCN1

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

RTECS 

NJ0621100

HS Code 

2933.99.6100

SERTINDOLE Usage And Synthesis

Description

Serdolect was launched in the UK for acute and chronic schizophrenia and schizoaffective psychoses. It is synthetically available in three steps from 5chloro-l- (4-fluorophenyl)-l H-indole. Sertindole is selective for the limbic areas of the brain and has a high affinity for the serotinin 5-HT₂ receptor where it behaves as an antagonist. It has weak affinity for the α₁-adrenergic receptor and no affinity for dopamine D₂ receptors. It is as effective as haloperidol but without the extrapyramidal symptoms. This may be a consequence of the fact that it expresses the c-fos protein in a manner different for haloperidol but similar to clozapine. It is non-sedating, long lasting (several days after a single dose) and has an atypical mode of action.

Description

Sertindole is an atypical antipsychotic that binds to dopamine D₂ receptors and the serotonin (5-HT) receptor subtypes 5-HT_1D, 5-HT_2A, and 5-HT_2C (K_ds = 2.7, 20, 0.14, and 6 nM, respectively). It also binds to histamine H₁ and α₁- and α₂-adrenergic receptors (K_ds = 320, 3.9, and 190 nM, respectively). In vivo, sertindole (10 mg/kg) increases extracellular dopamine, acetylcholine (ACh), and glutamate levels in the medial prefrontal cortex in conscious rats. Sertindole (2.5 mg/kg) reverses ketamine-induced impairments in the extradimensional shift stage of the attentional set-shifting task (ASST) in rats. It reverses phencyclidine (PCP)-induced selective reversal learning deficits in rats and subchronic PCP-induced deficits in the novel object recognition task in mice. Sertindole (0.02-0.32 mg/kg) also prevents accuracy deficits and anticipatory over-responding in the 5-choice serial reaction time task (5CSRTT) induced by the NMDA receptor antagonist (R)-CPP in rats. Formulations containing sertindole have been used in the treatment of schizophrenia.

Chemical Properties

Off-White to Pale Yellow Solid

Originator

Lundbeck (Denmark)

Uses

antipsychotic;Dopamine D2/Serotonin 5-HT2 receptor antagonist

Uses

Antipsychotic used in the treatment of schizophrenia.

Definition

ChEBI: A phenylindole that is 1H-indole which is substituted on the nitrogen by a p-chlorophenyl group, at position 5 by chlorine, and at position 3 by a piperidin-4-yl group, which is itself substituted on the nitrogen by a 2-(2-o oimidazolidin-1-yl)ethyl group.

brand name

SerLect (Abbott).

Side effects

Sertindole is an indole-containing compound that behaves as a high-affinity serotonin 5-HT2 receptor antagonist, with weak affinity for adrenergic α1 receptors and almost no affinity for dopaminergic D2 receptors. It is about as effective as haloperidol in the treatment of acute and chronic schizophrenia, but with much lower incidence of extrapyramidal side effects. Sertindole is relatively nonsedating, and its effects are long lasting (several days).

References

[1] B CUSACK  E R  A Nelson. Binding of antidepressants to human brain receptors: focus on newer generation compounds.[J]. Psychopharmacology, 1994, 114 4: 559-565. DOI: 10.1007/bf02244985
[2] ARNE M?RK  J?rn A  Louise M Witten. Effect of sertindole on extracellular dopamine, acetylcholine, and glutamate in the medial prefrontal cortex of conscious rats: a comparison with risperidone and exploration of mechanisms involved.[J]. Psychopharmacology, 2009, 206 1: 39-49. DOI: 10.1007/s00213-009-1578-4
[3] AGNIESZKA NIKIFORUK  Piotr P. Effects of quetiapine and sertindole on subchronic ketamine-induced deficits in attentional set-shifting in rats.[J]. Psychopharmacology, 2012: 65-74. DOI: 10.1007/s00213-011-2487-x
[4] NAGI IDRIS. Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory deficits in rodents: involvement of 5-HT(6) and 5-HT (2A) receptor mechanisms.[J]. Psychopharmacology, 2010, 208 1: 23-36. DOI: 10.1007/s00213-009-1702-5
[5] MIRJANA CARLI. Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP.[J]. Psychopharmacology, 2011, 214 3: 625-637. DOI: 10.1007/s00213-010-2066-6

SERTINDOLE(106516-24-9)Related Product Information

• Penfluridol
• CHEMBRDG-BB 4013121
• 5-CHLORO-1-METHYLINDOLE
• 5-CHLORO-1-(4-FLUORO-PHENYL)-1H-INDOLE
• 1-(4-FLUOROPHENYL)PYRROLE
• 5-CHLORO-3-(1-METHYL-4-PIPERIDINYL)INDOLE
• N-(PIPERIDINOETHYL)ETHYLENEDIAMINE
• 5-CHLORO-1-(4-FLUORO-PHENYL)-3-PIPERIDIN-4-YL-1H-INDOLE
• 3-Piperidin-4-yl-1H-indole
• 3-(1-METHYL-4-PIPERIDINYL)INDOLE
• SERTINDOLE
• 1-(2-AMINOETHYL)-2-IMIDAZOLIDONE