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-HT1D, 5-HT2A, and 5-HT2C (Kds = 2.7, 20, 0.14, and 6 nM, respectively). It also binds to histamine H1 and α1- and α2-adrenergic receptors (Kds = 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
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.
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).
