Sertindole

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.

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.

Off-White to Pale Yellow Solid

Lundbeck (Denmark)

antipsychotic;Dopamine D2/Serotonin 5-HT2 receptor antagonist

Antipsychotic used in the treatment of schizophrenia.

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.

SerLect (Abbott).

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).

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