Methylamine and benzylamine induced hypophagia in mice: Modulation by semicarbazide-sensitive benzylamine oxidase inhibitors and aODN towards Kv1.1 channels

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 (NH4 +) and of the anoressants amphetamine (AMPH) and nicotine (NIC). After i.c.v. administration, an approximate ranking order of potency was: ChTX5AMPH4NIC=TEA5GLI5MET4BZ4NH4 +. 2 Clorgyline (2.5 mg kg71 i.p.) or deprenyl (10 mg kg71 i.p.) potentiated the anorectic e ect of i.c.v.-administered BZ, NIC and AMPH. The e ect of TEA was increased only by deprenyl, while MET, NH4 +, ChTX and GLI were not a ected by either of the inhibitors. 3 The Bz-SSAO inhibitors a-aminoguanidine (50 mg kg71 i.p.), B24 (100 mg kg71 i.p.) and MDL 72274 (2.5 mg kg71 i.p.) potentiated the e ect of i.p., but not of i.c.v.-administered MET. 4 Antisense oligodeoxyribonucleotides (aODN) to Kv1.1 potassium channels abolished the e ect of BZ and TEA, but was ine ective in reducing the activity of MET and other compounds. 5 These results suggest that MET is endowed with peculiar hypophagic e ects at dosage levels that are not able to a ect gross behaviour in mice. The e ect of MET, di erently 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.