CNS-targeting pharmacological interventions for the metabolic syndrome

Abstract

Conflict of interest: RDD is currently an employee of Novo Nordisk. RDD is a cofounder of Marcadia, a company that pioneered the discovery of glucagon mixed agonists. It was acquired by Roche and later Novo Nordisk. He is a coinventor on multiple patents owned by Indiana University. MHT is a scientific advisor for Erx Biotech.

Microglia–Neuron Crosstalk in Obesity: Melodious Interaction or Kiss of Death?

“…New pharmacological tools that selectively and safely target hypothalamic neuronal circuits affected by obesity are on the horizon [ 38 , 104 ]. However, the cellular and molecular mechanisms leading to hypothalamic neurons’ dysfunction in obesity have only begun to emerge, and additional research will be needed before functional optimization and clinical translation of these brain-directed agents.…”

Potential Role of Dexamphetamine in the Treatment of Non-alcoholic Fatty Liver Disease: Hopes and Pitfalls

“…Elevated release of monoamines promotes satiety and reduces feeding through the activation of postsynaptic α-and β-adrenergic receptors and D1/D2 receptors. 21 The d-isomer of amphetamine is more potent than its I-isomer. 22 It has an extensive distribution in most of the tissues and possesses a potent psycho-stimulant effect.…”

“…Hypertension and cardiac arrhythmias can occur at higher doses, but they tend to resolve after dose reduction. 21,35 A study by Williams et al showed that dexamphetamine has been a less commonly abused drug compared to abuse of other substances. 35 Apart from this, dexamphetamine can lead to some clinically significant drug interactions with drugs such monoamine oxidase inhibitors; antacids and other drugs used for peptic ulcers; antipsychotics, such as chlorpromazine and haloperidol; norepinephrine; and anticonvulsants, such as phenytoin and phenobarbital.…”

Un analogue du glucagon-like peptide 1 (GLP1) administré par voie orale

“…Ces deux modifications contribuent à prolonger la durée d'action du peptide, qui est de 8 jours pour le sémaglutide injectable, alors qu'elle n'est que de quelques minutes pour le GLP1 natif. La formulation du sémaglutide pour prise orale associe le peptide le N-[8 (2-hydroxylbenzoyl) amino] hormones [8]. Des agonistes spécifiques des récepteurs du GLP1 (aGLP1) ont également été développés, ainsi que des inhibiteurs de la dipeptidyl peptidase 4 (DPP4), la principale enzyme responsable du catabolisme du GLP1 et du GIP.…”