5-HT1B receptor binding in degenerative movement disorders

Castro, Elena; Pascual, Julio; Romón, Tamara; Berciano, José; Figols, J.; Pazos, Ángel

doi:10.1016/s0006-8993(97)01566-7

Cited by 57 publications

(30 citation statements)

References 17 publications

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“…The first possibility was that 5-HT suppresses GABAergic inhibitory responses to cortical stimulation through presynaptic 5-HT 1B receptors, which are densely expressed on axons and axon terminals in the pallidum (Bonaventure et al, 1998;Castro et al, 1998;Riad et al, 2000;Sari, 2004;Mostany et al, 2005). A 5-HT 1B receptor agonist inhibited 3 H-GABA release from rat GPe slices (Chadha et al, 2000), and activation of presynaptic 5-HT 1B receptors suppresses GABAergic inhibition in other brain areas (Pickard et al, 1999;Matsuoka et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The literature suggests that serotonin (5-HT) actions in the pallidum exert significant roles in movement control (Castro et al, 1998;Doder et al, 2003;Jackson et al, 2004). Anatomical studies have shown that both segments of the pallidum receive abundant 5-HT innervations from the dorsal raphe (Pasik et al, 1984;Vertes, 1991;Charara and Parent, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…(1) 5-HT suppresses GABAergic inhibitions through presynaptic 5-HT 1B receptors, which are densely expressed in axons and axon terminals in the pallidum (Bonaventure et al, 1998;Castro et al, 1998;Riad et al, 2000;Sari, 2004;Mostany et al, 2005). Activation of 5-HT 1B receptors inhibited 5-HT decreases the firing of pallidal neurons through postsynaptic 5-HT 1A receptors.…”

Section: Introductionmentioning

confidence: 99%

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Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey

Kita¹,

Chiken²,

Tachibana³

et al. 2007

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey

Kita¹,

Chiken²,

Tachibana³

et al. 2007

J. Neurosci.

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“…It should be noted that there is extensive evidence for the loss of 5-HT neurons in PD (D'Amato et al, 1987), including the loss of 5-HT nerve terminals and diminished levels of 5-HT transporter binding sites in the striatum. Loss of presynaptic 5-HT neurons would be expected to cause supersensitivity of post-synaptic 5-HT 2A receptors, whose density has been reported in one study to be reduced by 50% (Chen et al, 1998), whereas the 5-HT 1B (Castro et al, 1998;Waeber and Palacios, 1989) and 5-HT 4 (Reynolds et al, 1995) receptor density has not been found to differ in post-mortem studies of PD patients from those of comparison groups. However, the number of subjects in these studies is quite small.…”

Section: Mechanism Of Action: 5-ht 2a Receptor Blockade and Diminishementioning

confidence: 91%

Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson's Disease Psychosis

Meltzer

Mills

Revell

et al. 2009

Neuropsychopharmacol

263

173

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Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT 2A ) receptor blockade. We postulated that pimavanserin (ACP-103), a highly selective 5-HT 2A inverse agonist, would attenuate psychosis in patients with PDP, but avoid motoric worsening and non-motoric side effects. In this double-blind, randomized multicenter 28-day study, the tolerability and efficacy of pimavanserin was compared with placebo in 60 patients with L-DOPA or dopamine (DA) agonist-induced PDP. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. Antipsychotic efficacy was evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS) and a UPDRS Part I psychosisrelevant item. Pimavanserin did not differentiate from placebo with regard to motor impairment, sedation, hypotension, or other side effects. The principal measures of efficacy of antipsychotic response to pimavanserin, the SAPS total domain score, only showed a trend. However, the pimavanserin-treated patients showed significantly greater improvement in some but not all measures of psychosis, including SAPS global measures of hallucinations and delusions, persecutory delusions, and the UPDRS measure of delusions and hallucinations. Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function, or cause sedation or hypotension Thus, pimavanserin may represent a novel treatment for PDP. Furthermore, these results support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT 2A receptor antagonism.

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“…Taken together, therefore, these data seem to suggest a presynaptic localization of 429 this receptor subtype, presumably on terminals of striatal afferents (Pazos et al, 1987a;Boschert et al, 1994;Bruinvels et al, 1994;Bonaventure et al, 1998;Sari et al, 1999;Varnas et al, 2001Varnas et al, , 2005, where it acts as heteroreceptor (Barnes and Sharp, 1999). Moreover, the levels of 5-HT 1B binding sites in these areas after selective lesion of nigral DAergic cells or striatal neurons, as well as radioligand studies on postmortem human brain of patients who had suffered degenerative movement disorders, clearly demonstrate the localization of this receptor on striatonigral and striatopallidal GABAergic afferents (Waeber et al, 1990b;Castro et al, 1998;Compan et al, 1998). Similarly to the 5-HT 1B subtype, radiolabelled sites for 5-HT 1D receptors were found in these structures, despite the lower densities as compared to the previous receptor (partially due to the lack of specific radioligand), while in situ hybridization studies showed a lack of its mRNA (Bruinvels et al, 1993a(Bruinvels et al, , 1994.…”

Section: Substantia Nigra and Globus Pallidusmentioning

confidence: 58%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

132

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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5-HT1B receptor binding in degenerative movement disorders

Cited by 57 publications

References 17 publications

Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey

Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey

Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson's Disease Psychosis

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

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