Effect of Adjunctive Treatment With Serotonin-1A Agonist Tandospirone on Memory Functions in Schizophrenia

Sumiyoshi, Tomiki; Matsui, Mié; Yamashita, Iwao; Nohara, Shigeru; Uehara, Takashi; Kurachi, Masayoshi; Meltzer, Herbert Y.

doi:10.1097/00004714-200006000-00019

Cited by 65 publications

(43 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 5-HT 1A agonist activity of SSR181507 might account for this positive aspect. This supposition is substantiated by the recent report that addition of the 5-HT 1A receptor partial agonist tandospirone to classical antipsychotics seems to improve some types of memory function deficits associated with schizophrenia (Sumiyoshi et al, 2000(Sumiyoshi et al, , 2001.…”

Section: Discussionmentioning

confidence: 85%

“…In the clinic, buspirone and tandospirone, two 5-HT 1A receptor partial agonists, have been shown to decrease parkinsonian signs or tardive dyskinesia in schizophrenic patients treated with antipsychotics (Goff et al, 1991;Moss et al, 1993;Yoshida et al, 1998). In addition, when added onto antipsychotics, tandospirone improved cognition in patients (Sumiyoshi et al, 2000(Sumiyoshi et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. II: Behavioral Profile Predictive of an Atypical Antipsychotic Activity

Depoortère

Boulay

Perrault

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

monohydrochloride) is a novel tropanemethanamine benzodioxane that displays antagonist activity at dopamine D 2 receptors and agonist activity at 5-HT 1A receptors. SSR181507 antagonized apomorphine-induced climbing in mice and stereotypies in rats (ED 50 of 2 and 3.4 mg/kg i.p., respectively) and blocked D-amphetamine-induced hyperlocomotion in rats at lower doses (0.3-1 mg/kg i.p.). At 1-10 mg/kg, it was found to disrupt active avoidance in mice. SSR181507 did not induce catalepsy in rats (MED460 mg/kg i.p.) and antagonized (3-10 mg/kg i.p.) haloperidol-induced catalepsy. SSR181507 was also active in two models sensitive to antidepressant/ anxiolytic drugs: in a guinea-pig pup/mother separation test, it decreased (1-3 mg/kg i.p.) the time spent vocalizing during the separation episode, and in a lithium-induced taste aversion procedure in rats, it partially reversed (3 mg/kg i.p.) the decrease of intake of a saccharin solution. Furthermore, SSR181507 increased (3 mg/kg i.p.) the latency time to paradoxical sleep in rats, an effect commonly observed with antidepressants. Coadministration of the selective 5-HT 1A blocker SL88.0338 produced catalepsy and antagonized the effects of SSR181507 in the depression/anxiety tests, confirming the view that activation of 5-HT 1A receptors confers an atypical profile on SSR181507, and is responsible for its antidepressant/anxiolytic properties. Finally, SSR181507 (1-3 mg/kg) did not affect memory performance in a Morris water maze task in rats. The pharmacological profile of SSR181507 suggests that it should control the symptoms of schizophrenia, in the absence of extrapyramidal signs and cognitive deficits, with the additional benefit of antidepressant/anxiolytic activities.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. II: Behavioral Profile Predictive of an Atypical Antipsychotic Activity

Depoortère

Boulay

Perrault

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…summarizes the mode of actions (agonism or antagonism) and specific compounds related to the above-mentioned 5-HT receptor subtypes. Among them, 5-HT 1A receptor stimulation is currently considered as the most promising approach (Llado-Pelfort et al 2011, Newman-Tancredi and Kleven 2011, Newman-Tancredi and Albert in press, Sumiyoshi C. et al 2006, Sumiyoshi T. et al 2007a, Sumiyoshi T. et al 2000, Sumiyoshi T. et al 2007b, Sumiyoshi T. et al 2001a, Sumiyoshi T. et al 2001b), as discussed in the next section. This is followed by 5-HT 2A antagonism, as elicited by certain (although not satisfactory) efficacy of a series of AAPDs whose principal pharmacologic feature is blockade of 5-HT 2A receptors (Meltzer et al 1989, Meltzer and Massey 2011, Stockmeier et al 1993, Sumiyoshi T. et al 1995.…”

Section: -Ht Receptors and Cognitive Functionmentioning

confidence: 99%

Serotonin-1A Receptors and Cognitive Enhancement in Schizophrenia: Role for Brain Energy Metabolism

Sumiyoshi¹,

Uehara²

2012

Schizophrenia in the 21st Century

Self Cite

View full text Add to dashboard Cite

“…Thus, DA D 2 receptor antagonists with high affinity and agonist properties at the 5-HT 1A receptor should have a low incidence of EPS. Moreover, recent work with tandospirone (Sumiyoshi et al, 2000(Sumiyoshi et al, , 2001 have suggested the usefulness of 5-HT 1A agonists for improving cognition in patients with schizophrenia. It has also been proposed that the ability of atypical antipsychotics to alleviate the negative and cognitive symptoms of schizophrenia is related to the fact that they enhance DA release in the medial prefrontal cortex (Kapur and Remington, 1996).…”

Section: Introductionmentioning

confidence: 99%

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

Claustre

Peretti

Brun

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT 1A receptors (K I ¼ 0.8, 0.2, and 0.2 nM for human D 2 , D 3 , and 5-HT 1A , respectively). In vivo, SSR181507 inhibited [ 3 H]raclopride binding to D 2 receptors in the rat (ID 50 ¼ 0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D 2 antagonist and 5-HT 1A agonist properties in the same concentration range in vitro (IC 50 ¼ 5.3 nM and EC 50 ¼ 2.3 nM, respectively, in the GTPgS model) and in the same dose range in vivo (ED 50 ¼ 1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D 2 receptor antagonism and 5-HT 1A agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia.

show abstract

Effect of Adjunctive Treatment With Serotonin-1A Agonist Tandospirone on Memory Functions in Schizophrenia

Cited by 65 publications

References 15 publications

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. II: Behavioral Profile Predictive of an Atypical Antipsychotic Activity

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. II: Behavioral Profile Predictive of an Atypical Antipsychotic Activity

Serotonin-1A Receptors and Cognitive Enhancement in Schizophrenia: Role for Brain Energy Metabolism

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

Contact Info

Product

Resources

About