Selective inhibition of amine oxidases differently potentiate the hypophagic effect of benzylamine in mice

Abstract

In mice deprived of food for 12 h, the i.c.v. or i.p. administration of benzylamine, a substrate common to both monoamine oxidase B and semicarbazide-sensitive benzylamine oxidases, dose-dependently inhibited feeding. This effect was significantly potentiated by selective monoamine oxidase A and B inhibition, suggesting that central monoamines, known to be substrates of these enzymes may be Ž . released. The i.p. administration of semicarbazide-sensitive benzylamine oxidase inhibitors, B24 3,5-ethoxy-4-aminomethylpyridine and ŽŽ . . MDL 72274 E -2-phenyl-3-chloroallylamine strongly potentiated the effect of i.p. but not i.c.v.-administered benzylamine. The hypophagic effect of benzylamine was evaluated following i.c.v. administration, in comparison with the effect of the sympathomimetic compound amphetamine or the K q channel blocker tetraethylammonium, as reference compounds. Our results make it possible to define benzylamine as a centrally acting hypophagic compound devoid of amphetamine-like motor stimulatory effects and point to a role of B24 and MDL 72274 as specific peripheral enhancers of the pharmacological effects of benzylamine. q

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

“…As reported previously in more detail (Banchelli et al, 2001), the observation that the hypophagic e ect of BZ is potentiated by both MAO A and MAO B inhibitors has been explained by the inhibition of the deamination of 5HT (MAO A substrate) or DA (MAO B substrate) probably released by BZ in the brain. Furthermore the selective inhibition of MAO B may e ectively increase the levels of unchanged BZ active in the brain.…”

“…Recently, this view has received some indirect experimental support from the observation that, when administered i.p., BZ displays a novel central hypophagic activity in mice only after pretreatment with the Bz-SSAO inhibitors B24 or MDL 72274. We have also observed that BZ induces its e ects probably by acting like the potassium channel blockers TEA or 4-aminopyridine (Pirisino et al, 1993;Banchelli et al, 2000;2001). In other investigations, it has been found that potassium channel blockers reduce food intake in mice by acting as depolarizing compounds in the brain.…”

“…One of the main purposes of this work was to verify the in¯uence of the selective inhibition of MAO A, MAO B and Bz-SSAO, respectively on the pharmacological activity of MET compared to that of BZ and other reference compounds, after clorgyline, deprenyl and MDL 72274 mice pretreatments. To this aim we used the same dosage schedule of the inhibitors previously reported to induce a selective and statistically signi®cant (more than 85%) inhibition of the appropriate AO subtype in the tissues of the mice (Banchelli et al, 2001). Depending on the absence of Bz-SSAO in the brain, the e ect of MET, injected directly into cerebral ventricles, was una ected by pretreatments with MDL 72274, a selective and irreversible inhibitor of these enzymes.…”

“…The i.p. pretreatment of mice with clorgyline (2.5 mg kg 71 ) or deprenyl (10 mg kg 71 ) to selectively inhibit MAO A or MAO B activities (Banchelli et al, 2001), did not a ect the basal food consumption of the controls, but di erently modi®ed the anorectic e ect of some i.c.v.-administered compounds. Namely, the anorectic e ect of BZ, AMPH and NIC was potentiated by clorgyline (40, 67 and 18% respectively) and deprenyl (64, 88 and 27% respectively), the e ect of TEA only by deprenyl (64%), while the activity of MET, ChTX, GLI remained completely unmodi®ed after selective MAOs inhibition (Table 1).…”

“…With regard to the dosage regimen of MDL 72274, B24 or AG as inhibitors of semicarbazide-sensitive benzylamine oxidases, the same dosage (2.5 mg kg 71 i.p. ; 100 mg kg 71 ; 50 mg kg 71 respectively) previously found to be e ective for these enzymes (Yu & Zuo, 1997;Banchelli et al, 2001) was given i.p. to the mice.…”