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Group III metabotropic glutamate (mGlu) receptors are localized in presynaptic terminals within basal ganglia (BG) circuitry that become hyperactive due to dopamine depletion in Parkinson's disease (PD). For this reason, group III mGlu receptors, in particular mGlu4, have been considered as key strategic targets for non-dopaminergic pharmacological(More)
BACKGROUND AND PURPOSE Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive(More)
LSP1-2111 is a group III metabotropic glutamate receptor agonist with preference toward the mGlu4 receptor subtype. This compound has been extensively used as a tool to explore the pharmacology of mGlu4 receptor activation in preclinical animal behavioral models. However, the blood-brain barrier penetration of this amino acid derivative has never been(More)
Previous studies demonstrated that the Group III mGlu receptor-selective orthosteric agonist, LSP1-2111 produced anxiolytic- but not antidepressant-like effects upon peripheral administration. Herein, we report the pharmacological actions of Lu AF21934, a novel, selective, and brain-penetrant positive allosteric modulator (PAM) of the mGlu(4) receptor in(More)
Harmaline induces tremor in animals resembling essential tremor which has been suggested to result from activation of the glutamatergic olivo-cerebellar projection. The aim of the present study was to examine the effects of systemic administration of Lu AF21934, a brain-penetrating positive allosteric modulator of the metabotropic glutamate receptor 4(More)
Metabotropic glutamate 4 (mGlu4) receptor is a promising target for the treatment of motor deficits in Parkinson's disease (PD). This is due in part to its localization at key basal ganglia (BG) synapses that become hyperactive in this pathology, particularly striatopallidal synapses. In this context, mGlu4 receptor activation using either orthosteric(More)
In this review, we aim to present, discuss and clarify our current understanding regarding the prediction of possible antipsychotic effects of metabotropic glutamate (mGlu) receptor ligands. The number of preclinical trials clearly indicates, that this group of compounds constitutes an excellent alternative to presently used antipsychotic therapy, being(More)
Diverse preclinical studies suggest the potential therapeutic utility of the modulation of the glutamatergic system in brain via metabotropic glutamate (mGlu) receptors. Lu AF21934, a positive allosteric modulator of the mGlu4 receptor, was previously shown to reverse behavioral phenotypes in animal models thought to mimic positive, negative, and cognitive(More)
Society expects that the wave of contemporary new discoveries in biological sciences will soon lead to novel treatments for human diseases, including many devastating brain disorders. Historically, medicinal chemists have contributed to drug discovery teams in ways that synergize with those from their partner sciences, and help transform new knowledge into(More)