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Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test.
Eur J Pharmacol. 2007 Oct 31; 572(2-3):160-70.EJ

Abstract

Lurasidone (SM-13496) is a novel atypical antipsychotic with high affinities to dopamine D2, serotonin 5-HT7, 5-HT2A, 5-HT1A receptors and alpha2C adrenoceptor. In this study, the effects of lurasidone on the rat passive-avoidance response and its impairment by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) were evaluated and compared with those of other antipsychotics. The passive-avoidance response was examined by measuring the step-through latency, 1 day after the animals received foot-shock training. When given before the training session, lurasidone did not affect the passive-avoidance response at any dose tested (1-30 mg/kg, p.o.). All the other atypical antipsychotics examined (i.e., risperidone, olanzapine, quetiapine, clozapine and aripiprazole), however, significantly reduced the step-through latency at relatively high doses. A pre-training administration of lurasidone significantly and dose-dependently reversed the MK-801-induced impairment of the passive-avoidance response. At doses lower than those that affected the passive-avoidance response, risperidone, quetiapine, and clozapine partially reduced the MK-801-induced impairment, whereas haloperidol, olanzapine, and aripiprazole were inactive. In addition, the post-training administration of lurasidone was as effective in countering the MK-801 effect as the pre-training administration, suggesting that lurasidone worked, at least in part, by restoring the memory consolidation process disrupted by MK-801. These results suggest that lurasidone is superior to other antipsychotics in improving the MK-801-induced memory impairment and may be clinically useful for treating cognitive impairments in schizophrenia.

Authors+Show Affiliations

Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd, Osaka, Japan. takeo-ishiyama@ds-pharma.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17662268

Citation

Ishiyama, Takeo, et al. "Lurasidone (SM-13496), a Novel Atypical Antipsychotic Drug, Reverses MK-801-induced Impairment of Learning and Memory in the Rat Passive-avoidance Test." European Journal of Pharmacology, vol. 572, no. 2-3, 2007, pp. 160-70.
Ishiyama T, Tokuda K, Ishibashi T, et al. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. Eur J Pharmacol. 2007;572(2-3):160-70.
Ishiyama, T., Tokuda, K., Ishibashi, T., Ito, A., Toma, S., & Ohno, Y. (2007). Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. European Journal of Pharmacology, 572(2-3), 160-70.
Ishiyama T, et al. Lurasidone (SM-13496), a Novel Atypical Antipsychotic Drug, Reverses MK-801-induced Impairment of Learning and Memory in the Rat Passive-avoidance Test. Eur J Pharmacol. 2007 Oct 31;572(2-3):160-70. PubMed PMID: 17662268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. AU - Ishiyama,Takeo, AU - Tokuda,Kumiko, AU - Ishibashi,Tadashi, AU - Ito,Akira, AU - Toma,Satoko, AU - Ohno,Yukihiro, Y1 - 2007/07/10/ PY - 2007/01/25/received PY - 2007/06/08/revised PY - 2007/06/12/accepted PY - 2007/7/31/pubmed PY - 2008/1/15/medline PY - 2007/7/31/entrez SP - 160 EP - 70 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 572 IS - 2-3 N2 - Lurasidone (SM-13496) is a novel atypical antipsychotic with high affinities to dopamine D2, serotonin 5-HT7, 5-HT2A, 5-HT1A receptors and alpha2C adrenoceptor. In this study, the effects of lurasidone on the rat passive-avoidance response and its impairment by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) were evaluated and compared with those of other antipsychotics. The passive-avoidance response was examined by measuring the step-through latency, 1 day after the animals received foot-shock training. When given before the training session, lurasidone did not affect the passive-avoidance response at any dose tested (1-30 mg/kg, p.o.). All the other atypical antipsychotics examined (i.e., risperidone, olanzapine, quetiapine, clozapine and aripiprazole), however, significantly reduced the step-through latency at relatively high doses. A pre-training administration of lurasidone significantly and dose-dependently reversed the MK-801-induced impairment of the passive-avoidance response. At doses lower than those that affected the passive-avoidance response, risperidone, quetiapine, and clozapine partially reduced the MK-801-induced impairment, whereas haloperidol, olanzapine, and aripiprazole were inactive. In addition, the post-training administration of lurasidone was as effective in countering the MK-801 effect as the pre-training administration, suggesting that lurasidone worked, at least in part, by restoring the memory consolidation process disrupted by MK-801. These results suggest that lurasidone is superior to other antipsychotics in improving the MK-801-induced memory impairment and may be clinically useful for treating cognitive impairments in schizophrenia. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17662268/Lurasidone__SM_13496__a_novel_atypical_antipsychotic_drug_reverses_MK_801_induced_impairment_of_learning_and_memory_in_the_rat_passive_avoidance_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00737-6 DB - PRIME DP - Unbound Medicine ER -