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-HT
2 receptor where it behaves as an
antagonist. It has weak affinity for the α
1-adrenergic receptor and no affinity for
dopamine D
2 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 D
2 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 H
1 and α
1- and α
2-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 MRK Jrn 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
