Metabotropic Glutamate Receptors: Novel Targets for Drug Development

• Published in: Journal of medicinal chemistry Vol. 38; no. 9; pp. 1417 - 1426
• Main Authors: Knoepfel, Thomas, Kuhn, Rainer, Allgeier, Hans
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.04.1995
• Subjects: Animals; Biological and medical sciences; Cloning, Molecular; Drug Design; Glutamatergic system (aspartate and other excitatory aminoacids); Humans; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Receptors, Metabotropic Glutamate - drug effects; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - physiology; Agonist; Psychotropic; Central nervous system; Glutamate receptor; Binding site; Review; In vitro; Signal transduction; α-Aminoacid; Cell line; Structure activity relation; Metabotropic receptor; Affinity; Antagonist; Mechanism of action
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00009a001

Glutamate receptors are classified into ionotropic and metabotropic glutamate receptors (mGluRs). Ionotropic glutamate receptors form ligand-gated ion channels and, thereby, directly mediate electrical signaling of nerve cells. mGluRs indirectly regulate electrical signaling by influencing intracellular metabolic processes via G-proteins. This perspective article focuses on the mGluR family. In particular, we discuss the structure of mGluRs and their functional properties in recombinant mammalian cells. We also report on the pharmacological properties of a variety of agonists and antagonists for mGluRs and their subtype specificity. Also discussed is the physiological role of mGluRs in the CNS and their possible involvement in pathophysiological processes. It will become apparent that mGluRs are equally promising as targets for drugs modulating glutamatergic synaptic transmission as are ionotropic glutamate receptors.