Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate - serotonin interactions for pharmacotherapy.
Based on 1) neuroanatomical and neuroimaging studies indicating aberrations in brain regions that are rich in glutamate neurons and 2) similarities between symptoms produced by N-methyl-D-aspartate (NMDA) antagonists in healthy subjects and those seen in autism, it is proposed in the present paper that infantile autism is a hypoglutamatergic disorder. Possible future pharmacological interventions in autism are discussed in the light of the intimate interplay between central glutamate and serotonin, notably the serotonin (5-HT) 2A receptor. The possible benefit of treatment with glutamate agonists [e.g. agents acting on the modulatory glycine site of the NMDA receptor, or so-called ampakines acting on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor] is discussed, as well as the potential usefulness of a selective 5-HT2A receptor antagonist.
Department of Pharmacology, University of Göteborg, Sweden.
M L
ML
Carlsson
D001321:Autistic Disorder / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use
D018691:Excitatory Amino Acid Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid