PMC:6218602 / 56451-57610
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6218602","sourcedb":"PMC","sourceid":"6218602","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6218602","text":"Drugs that can downregulate presynaptic disinhibited glutamate release on secondary downstream glutamate neurons have also been explored in patients with TRS and may also work to modulate circuit connectivity. Lamotrigine, an anticonvulsant drug that suppresses presynaptic glutamate release by the blockade of voltage-sensitive sodium channels has been shown to improve clinical response when used as an adjunct to clozapine treatment in ultra-resistant schizophrenia (138, 174–178). The beneficial effects may be associated with clozapine's low affinity to the D2-receptor and involvement with the glutamate system (in comparison to other antipsychotic drugs) which may be further enhanced by lamotrigine (138, 175). More recent clinical trials have studied the efficacy between the metabotropic glutamate 2/3 (mGlu2/3) receptor agonist pomaglumetad methionil (also known as LY2140023) and atypical antipsychotics (138, 179, 180). In a phase II study, it was found to be less effective than the comparator atypical antipsychotic (180) and Eli Lilly subsequently stopped a phase III trial investigating the compound as it failed to meet its primary endpoint.","tracks":[{"project":"2_test","denotations":[{"id":"30425662-10530638-41865507","span":{"begin":475,"end":478},"obj":"10530638"},{"id":"30425662-11769825-41865507","span":{"begin":475,"end":478},"obj":"11769825"},{"id":"30425662-14643092-41865507","span":{"begin":475,"end":478},"obj":"14643092"},{"id":"30425662-15364042-41865507","span":{"begin":475,"end":478},"obj":"15364042"},{"id":"30425662-17383857-41865507","span":{"begin":475,"end":478},"obj":"17383857"},{"id":"30425662-11769825-41865508","span":{"begin":713,"end":716},"obj":"11769825"},{"id":"30425662-17767166-41865509","span":{"begin":922,"end":925},"obj":"17767166"},{"id":"30425662-21508856-41865510","span":{"begin":927,"end":930},"obj":"21508856"},{"id":"30425662-21508856-41865511","span":{"begin":1032,"end":1035},"obj":"21508856"}],"attributes":[{"subj":"30425662-10530638-41865507","pred":"source","obj":"2_test"},{"subj":"30425662-11769825-41865507","pred":"source","obj":"2_test"},{"subj":"30425662-14643092-41865507","pred":"source","obj":"2_test"},{"subj":"30425662-15364042-41865507","pred":"source","obj":"2_test"},{"subj":"30425662-17383857-41865507","pred":"source","obj":"2_test"},{"subj":"30425662-11769825-41865508","pred":"source","obj":"2_test"},{"subj":"30425662-17767166-41865509","pred":"source","obj":"2_test"},{"subj":"30425662-21508856-41865510","pred":"source","obj":"2_test"},{"subj":"30425662-21508856-41865511","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecbf93","default":true}]}]}}