ArticlePsychopharmacology2018
Effects of the T-type calcium channel antagonist Z944 on paired associates learning and locomotor activity in rats treated with the NMDA receptor antagonist MK-801.
Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 12 citations in OpenAlex.
- Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944.The Journal of general physiology · 2026Article
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- Pharmacologically induced N-methyl-D-aspartate receptor hypofunction impairs goal-directed food seeking in rats.Neuropsychopharmacology reports · 2021Article
- SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppInternational journal of molecular sciences · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleCurrently available antipsychotics are unsatisfactory given their side effects and limited efficacy for the cognitive symptoms of schizophrenia. Many currently available drugs, such as haloperidol, are T-type calcium channel antagonists in addition to their well-established antagonism of dopamine D2 receptors. Thus, preclinical research into the effects of T-type calcium channel antagonists/blockers in behavioral assays related to schizophrenia may inform novel therapeutic strategies.
objectivesWe explored the effects of a recently developed highly selective T-type calcium channel antagonist, Z944 (2.5, 5.0, 10.0 mg/kg), on the MK-801 (0.15 mg/kg) model of acute psychosis.
methodsTo examine the effects of Z944 on behaviors relevant to schizophrenia, we tested touchscreen-based paired associates learning given its relevance to the cognitive symptoms of the disorder and locomotor activity given its relevance to the positive symptoms.
resultsAcute treatment with Z944 failed to reverse the visuospatial associative memory impairments caused by MK-801 in paired associates learning. The highest dose of drug (10.0 mg/kg) given alone produced subtle impairments on paired associates learning. In contrast, Z944 (5.0 mg/kg) blocked the expected increase in locomotion following MK-801 treatment in a locomotor assay.
conclusionsThese experiments provide support that Z944 may reduce behaviors relevant to positive symptoms of schizophrenia, although additional study of its effects on cognition is required. These findings and other research suggest T-type calcium channel antagonists may be an alternative to currently available antipsychotics with less serious side effects.
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