SERTINDOLE

Absorption

Orally available.

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)

The Uses of SERTINDOLE

Antipsychotic used in the treatment of schizophrenia.

The Uses of SERTINDOLE

antipsychotic;Dopamine D2/Serotonin 5-HT2 receptor antagonist

What are the applications of Application

Sertindole is a SR-2 (5-HT2) and D2DR (D2 receptor) antagonist

Background

Sertindole, a neuroleptic, is one of the newer antipsychotic medications available. Serdolect is developed by the Danish pharmaceutical company H. Lundbeck. It is a phenylindole derivative used in the treatment of schizophrenia. It was first marketed in 1996 in several European countries before being withdrawn two years later because of numerous cardiac adverse effects. It has once again been approved and should soon be available on the French and Australian market.

Indications

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).

Pharmacokinetics

Sertindole is an atypical antipsychotic at least as effective as haloperidol and risperidone in the treatment of neuroleptic-responsive schizophrenia. Sertindole improves negative symptoms, and is also effective for the treatment of neuroleptic-resistant schizophrenia. Sertindole is generally well tolerated and is associated with a low rate of extrapyramidal symptoms (EPS).

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).

Metabolism

Hepatic. Sertindole is metabolized by cytochrome P450 isoenzymes CYP 2D6 and CYP 3A4.