The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64 766) in the treatment of chronic psychosis

Castelão, JoséFrancisco; Ferreira, Luiz Danilo Damasceno; Gelders, Y; Heylen, S

doi:10.1016/0920-9964(89)90034-0

Cited by 93 publications

(34 citation statements)

References 22 publications

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“…Our results show that more than one component of the 5-HT systems is directly altered in schizophrenia, with increased 5-HT receptor number in several limbic regions. A supersen sitive 5-HT system in schizophrenia is suggested by the evidence that compounds with antiserotonergic prop erties have antipsychotic properties (Castelaoo et al 1989;Meltzer et al 1989;Vinar et al . 1989) .…”

Section: Discussionmentioning

confidence: 99%

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Joyce

Shane

Lexow

et al. 1993

Neuropsychopharmacol

329

142

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Serotonin (5-HT) uptake sites were mapped by autoradiographic means with PH]cyano-imipramine , the 5-HTIA receptor with [3HJ8-hydroxy-2-[di-n-propyl-amino]tetralin ([3HJ8-0H-DPAT), and the 5-HTz receptor with both pH]ketanserin and {l251]1ysergic acid diethylamide ([lZ5IJLSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomallmatrix campartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern � either 5-HTz or 5-HTIA receptors. For the isocortex, a general organizational scheme was observed with the 5-HTIA receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the cambined distributions of the 5-HTIA receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was camplementary to the distribution of 5-HTIA and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomallmatrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HTIA receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HTIA receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotoninz receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n "" 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.

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Section: Discussionmentioning

confidence: 99%

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Joyce

Shane

Lexow

et al. 1993

Neuropsychopharmacol

329

142

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“…A recent advance in this field is the clinical introduction of compounds that have both dopamine-D2 and 5-HT 2A receptor antagonist properties, such as risperidone and clozapine. Such compounds are thought to be efficacious in treating the negative symptoms of chronic schizophrenia (Gelenberg & Doller, 1979;Ceulemans et al, 1985;Castelao et al, 1989;Gelders, 1989;Lieberman et al, 1989;Noda et al, 1993;Oka et al, 1993). In addition, the 5-HT2A antagonist, ritanserin, when combined with typical antipsychotics, has been reported to ameliorate the negative symptoms of schizophrenia (Gelders et al, 1985).…”

Section: Effects Of Antipsychotics On the Pcp-induced Enhancement Of mentioning

confidence: 99%

Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia

Noda

Yamada

Furukawa

et al. 1995

British J Pharmacology

212

124

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1 Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans.2 Repeated treatment with PCP (10 mg kg-' day-', s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-', s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-' day-', s.c., once a day for 14 days). 3 The enhancing effect of PCP (10 mg kg-' day-', s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 5 The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-', p.o.), risperidone (0.3 mg kg-', p.o.), and clozapine (3 and 10 mg kg-', p.o.), whereas haloperidol (0.3 and 1 mg kg-', p.o.) had no effect. 6 These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.

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“…Subse-quently, risperidone and other agents were synthesized which retained a high affinity for both dopamine and 5-HT2 receptors , to ensure an efficacious treatment of both the positive and negative symptoms, with beneficial effects on mood and anxiety, and little extrapyramidal disturbance (Castelao et al, 1989;Messoten et al, 1989;Meco et al, 1989;Leysen et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor antagonists in modifying rodent responding to aversive situations

Costall

Naylor

1995

British J Pharmacology

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1 The ability of 5-hydroxytryptophan, 5-HT2 receptor antagonists and typical and atypical neuroleptic agents to modify behavioural responding to aversive situations was investigated in the mouse light/dark test and rat social interaction. 2 The administration of 5-hydroxytryptophan inhibited rat social interaction and the exploratory behaviour of mice in the light/dark test.3 The 5-HT2 receptor antagonists, ketanserin, ritanserin, MDL11939, methysergide and RP62203, the neuroleptic agents, spiperone, haloperidol and benperidol, and the atypical neuroleptic agent, clozapine, when administered alone failed to modify mouse or rat behaviour. In contrast, when administered alone, sulpiride in rats and mice and thioridazine in rats disinhibited behaviour. 4 Methysergide, RP62203, ketanserin, ritanserin and MDL11939 antagonized the inhibitory effects of 5-hydroxytryptophan or reversed the inhibitory effects to one of disinhibition. 5 Low doses of spiperone (but not haloperidol or benperidol) also antagonized the inhibitory effects of 5-hydroxytryptophan in the rat but not the mouse. Higher doses of the three neuroleptic agents caused locomotor depression in both rats and mice which obscured any specific changes in behavioural responding to the aversive situations. 6 The disinhibitory profile of sulpiride in both mice and rats and thioridazine in rats was evident during their interaction with 5-hydroxytryptophan. Thioridazine in the mouse and clozapine in rats and mice also reversed the inhibitory effects of 5-hydroxytryptophan to one of disinhibition. 7 In summary, we present evidence that the atypical neuroleptic agents, thioridazine and clozapine, with their known affinity for the 5-HT2 receptors, can mimic the actions of reference 5-HT2 receptor antagonists to antagonize the inhibitory effects of 5-hydroxytryptophan in rodent models of anxiety. The results are intepreted in terms of drug action on different 5-HT2 and other 5-HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained.

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The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64 766) in the treatment of chronic psychosis

Cited by 93 publications

References 22 publications

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia

Behavioural interactions between 5‐hydroxytryptophan, neuroleptic agents and 5‐HT receptor antagonists in modifying rodent responding to aversive situations

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