4-methyl benzylamine stimulates food consumption and counteracts the hypophagic effects of amphetamine acting on brain Shaker-like Kv1.1 channels.
1.--4-methyl benzylamine (4-MBZ; 28 microg, 231 nmol) elicits a hyperphagic response in starved mice in contrast to the hypophagia induced by the parent compound benzylamine (BZ; 33 microg, 231 nmol) or by amphetamine (AMPH, 2 mug). 2.--In mice starved for only 4 h, and therefore with little stimulation to eat, the maximal increase in food consumption induced by intracerebroventricular (i.c.v.)-injected 4-MBZ was 190% over that of the controls (ED(50) 8.3+/-2.7 microg mouse(-1); 68+/-22 nmol mouse(-1)), whereas after i.p. administration, these values were 160% and approximately 129 mg kg(-1), respectively. 3.--The hyperphagic effect of 4-MBZ was reduced by more than 60% in mice pretreated with antisense oligodeoxyribonucleotide (aODN(1)) previously found to selectively inhibit (over 50%) the expression of Shaker-like Kv1.1 channels. 4.--In mice highly stimulated to eat after 12-h fasting, 4-MBZ (28 microg) significantly reduced (to about 70%) the hypophagic response by AMPH (2 microg) or BZ (33 microg). Conversely, these two compounds reduced (respectively, by 69 and 44%) the hyperphagic response of 4-MBZ in 4-h fasting mice. 5.--4-MBZ (28 microg) also reduced the hypermotility and the stimulation of inspection activity elicited by AMPH in mice and the release of DA stimulated by AMPH (2 microg) from the nucleus accumbens of rats. We hypothesize that 4-MBZ elicits hyperphagic effects probably by opening Shaker-like Kv1.1 subtypes in the brain, whereas AMPH and BZ are hypophagic by blocking these channels.
Pirisino
Renato
R
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, Florence 50134, Italy. renato.pirisino@unifi.it
Galeotti
Nicoletta
N
Livi
Silvia
S
Raimondi
Laura
L
Ghelardini
Carla
C
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D051662:Kv1.1 Potassium Channel / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats
D001067:Appetite Depressants; D019167:Appetite Stimulants; D001596:Benzylamines; D000697:Central Nervous System Stimulants; C063400:4-methylbenzylamine; D051662:Kv1.1 Potassium Channel; C030796:benzylamine; D000661:Amphetamine; D004298:Dopamine