title: Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport.
abstract: 1 Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. 2 The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). 3 Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. 4 There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. 5 Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis.
authors.affiliation: Physiology Division, Centre for Vascular Biology and Medicine, King's College London, Guy's Campus, New Hunt's House, London SE1 1UL. Richard.Naftalin@kcl.ac.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Naftalin
authors.forename: Philip
authors.initials: P
authors.lastname: Cunningham
authors.forename: Iram
authors.initials: I
authors.lastname: Afzal-Ahmed
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001692:Biological Transport; D002478:Cells, Cultured; D003975:Diazepam / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D019004:Galanin / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006801:Humans; D008550:Melatonin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D010889:Piracetam / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D017385:Sequence Homology; D013329:Structure-Activity Relationship; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001463:Barbiturates; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D018697:Nootropic Agents; D011963:Receptors, GABA-A; C495677:SLC2A1 protein, human; C495679:Slc2a1 protein, rat; D013973:Thyrotropin-Releasing Hormone; D019004:Galanin; D005947:Glucose; D008550:Melatonin; D003975:Diazepam; D010889:Piracetam