title: Investigations on the binding properties of the nootropic agent pyroglutamic acid.
abstract: The two stereoisomers of pyroglutamic acid (PCA), a nootropic or cognition-enhancing agent, and classic reference compounds were investigated for their ability to interact with 27 neurotransmitter receptors and drug binding sites prepared from selected areas of the central nervous system and labelled with high affinity and selectivity with specific radioligands. L-PCA significantly interacted with the rat forebrain excitatory amino acid receptors labelled with 3H-L-glutamic acid. The IC50 of L-PCA was 28.11 microM, that of cold L-glutamic acid was 1.68 microM. The corresponding figure for L-aspartic acid was 16.95 microM. The indirect Hill plot gave coefficients of 0.48, 1.08 and 0.75 for L-PCA, L-glutamic and L-aspartic acids, respectively. Only very high concentrations (10(-4) M) of L-PCA were able to slightly antagonize the specific binding of 3H-clonidine to alpha 2-adrenergic receptors, of 3H-dihydroalprenolol to beta 1- and beta 2-adrenergic receptors of the heart and of the lung and of 3H-diazepam to benzodiazepine receptors. The D-isomer of PCA was practically as active as the L-isomer on these receptors. Finally, L-PCA (10(-5) to 10(-4) M) was unable to antagonize the specific binding of all the other radioligands to their respective receptors and binding sites. D-PCA did not significantly interact with excitatory amino acid receptors or with any of the other sites studied here.
authors.affiliation: Institute of Biomedical Research A. Marxer R.B.M. SpA, Ivrea (TO), Italy.
authors.forename: D
authors.initials: D
authors.lastname: Barone
authors.forename: G
authors.initials: G
authors.lastname: Spignoli
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D018118:Chloride Channels; D003000:Clonidine / Q000037:antagonists & inhibitors; D003975:Diazepam / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006168:Guinea Pigs; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008803:Mianserin / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D011968:Receptors, Histamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D002121:Calcium Channel Blockers; D018118:Chloride Channels; D005971:Glutamates; D008565:Membrane Proteins; D011760:Pyrrolidinones; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D011983:Receptors, Purinergic; D011985:Receptors, Serotonin; D008803:Mianserin; D018698:Glutamic Acid; D003000:Clonidine; D003975:Diazepam; D011761:Pyrrolidonecarboxylic Acid