4‐methyl benzylamine stimulates food consumption and counteracts the hypophagic effects of amphetamine acting on brain Shaker‐like Kv1.1 channels

• Published in: British journal of pharmacology Vol. 147; no. 2; pp. 218 - 224
• Main Authors: Pirisino, Renato, Galeotti, Nicoletta, Livi, Silvia, Raimondi, Laura, Ghelardini, Carla
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2006; Nature Publishing; Nature Publishing Group
• Subjects: Amphetamine; Amphetamine - pharmacology; Animals; Appetite Depressants - pharmacology; Appetite Stimulants - administration & dosage; Appetite Stimulants - pharmacology; Benzylamines - administration & dosage; Benzylamines - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Central Nervous System Stimulants - pharmacology; dopamine; Dopamine - metabolism; Eating - drug effects; food consumption; Injections, Intraperitoneal; Injections, Intraventricular; Kv1.1 channels; Kv1.1 Potassium Channel - biosynthesis; Male; Medical sciences; Mice; Microdialysis; Motor Activity - drug effects; Nucleus Accumbens - metabolism; Pharmacology. Drug treatments; Rats; Amphetamine derivatives; Dopamine; CNS stimulant; Psychotropic; Central nervous system; Catecholamine; Encephalon; Amphetamine; Neurotransmitter; food consumption; Amfetamine; Food; Kv1.1 channels
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706465

4‐methyl benzylamine (4‐MBZ; 28 μg, 231 nmol) elicits a hyperphagic response in starved mice in contrast to the hypophagia induced by the parent compound benzylamine (BZ; 33 μg, 231 nmol) or by amphetamine (AMPH, 2 μg).
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 (ED50 8.3±2.7 μg mouse−1; 68±22 nmol mouse−1), whereas after i.p. administration, these values were 160% and approximately 129 mg kg−1, respectively.
The hyperphagic effect of 4‐MBZ was reduced by more than 60% in mice pretreated with antisense oligodeoxyribonucleotide (aODN1) previously found to selectively inhibit (over 50%) the expression of Shaker‐like Kv1.1 channels.
In mice highly stimulated to eat after 12‐h fasting, 4‐MBZ (28 μg) significantly reduced (to about 70%) the hypophagic response by AMPH (2 μg) or BZ (33 μg). Conversely, these two compounds reduced (respectively, by 69 and 44%) the hyperphagic response of 4‐MBZ in 4‐h fasting mice.
4‐MBZ (28 μg) also reduced the hypermotility and the stimulation of inspection activity elicited by AMPH in mice and the release of DA stimulated by AMPH (2 μg) 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.
British Journal of Pharmacology (2006) 147, 218–224. doi:10.1038/sj.bjp.0706465