title: Methylamine and benzylamine induced hypophagia in mice: modulation by semicarbazide-sensitive benzylamine oxidase inhibitors and aODN towards Kv1.1 channels.
abstract: 1. In starved mice, the anorectic activity of methylamine (MET) and benzylamine (BZ), both substrates of semicarbazide-sensitive benzylamine oxidases (Bz-SSAO), was compared with that of the potassium channel blocking agents charybdotoxin (ChTX), tetraethylammonium (TEA), gliquidone (GLI), ammonium chloride (NH(4)(+)) and of the anoressants amphetamine (AMPH) and nicotine (NIC). After i.c.v. administration, an approximate ranking order of potency was: ChTX> or =AMPH>NIC=TEA> or =GLI> or =MET>BZ>NH(4)(+). 2. Clorgyline (2.5 mg kg(-1) i.p.) or deprenyl (10 mg kg(-1) i.p.) potentiated the anorectic effect of i.c.v.-administered BZ, NIC and AMPH. The effect of TEA was increased only by deprenyl, while MET, NH(4)(+), ChTX and GLI were not affected by either of the inhibitors. 3. The Bz-SSAO inhibitors alpha-aminoguanidine (50 mg kg(-1) i.p.), B24 (100 mg kg(-1) i.p.) and MDL 72274 (2.5 mg kg(-1) i.p.) potentiated the effect of i.p., but not of i.c.v.-administered MET. 4. Antisense oligodeoxyribonucleotides (aODN) to Kv1.1 potassium channels abolished the effect of BZ and TEA, but was ineffective in reducing the activity of MET and other compounds. 5. These results suggest that MET is endowed with peculiar hypophagic effects at dosage levels that are not able to affect gross behaviour in mice. The effect of MET, differently from BZ, seems unrelated to an increase in the central release of monoaminergic mediators, as well as to a Kv1.1 blocking activity. Through a reduction of the endogenous breakdown of MET, Bz-SSAO inhibitors enhance the central pharmacological activity of this amine.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Viale Pieraccini, 6, 50134 Florence, Italy. Pirisino@server1.Pharm.Unifi.it
authors.forename: R
authors.initials: R
authors.lastname: Pirisino
authors.forename: C
authors.initials: C
authors.lastname: Ghelardini
authors.forename: G
authors.initials: G
authors.lastname: Banchelli
authors.forename: N
authors.initials: N
authors.lastname: Galeotti
authors.forename: L
authors.initials: L
authors.lastname: Raimondi
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D001595:Benzylamine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001596:Benzylamines / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007276:Injections, Intraventricular; D051662:Kv1.1 Potassium Channel; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011437:Propylamines / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D000498:Allyl Compounds; D001596:Benzylamines; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D006146:Guanidines; C496947:Kcna1 protein, mouse; C090015:MDL 72274A; D008744:Methylamines; D008996:Monoamine Oxidase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011437:Propylamines; D012663:Semicarbazides; D013453:Sulfonylurea Compounds; D000643:Ammonium Chloride; D018999:Charybdotoxin; D051662:Kv1.1 Potassium Channel; C010059:carbamylhydrazine; D019789:Tetraethylammonium; C030796:benzylamine; C027451:methylamine; C010969:gliquidone; D000661:Amphetamine; D001595:Benzylamine Oxidase; C004479:pimagedine