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Alzheimer's Disease
Published in Marc E. Agronin, Alzheimer's Disease and Other Dementias, 2014
Several agents have been studied that prevent the aggregation of Ab42 into protein fibrils that form neuritic plaques. Tramiprosate (also known as homotaurine) is a small organic molecule that binds to Ab and prevents fibrillization, and it may also have anti-inflammatory properties. A 3-month, double-blind, placebo-controlled Phase II trial with a 36-month open label extension of tramiprosate in mild to moderately impaired AD sufferers showed a significant reduction in CSF Ab42 and a decline in cognitive deterioration, although no clear cognitive improvement on the main outcome measures (Aisen et al., 2007). A larger clinical trial of over 1,000 AD patients also failed to show significant improvement in cognition, although there was a trend toward improvement and less hippocampal volume loss in treated subjects (Aisen et al., 2011). Tramiprosate is no longer in clinical trials but is being sold in Canada and Europe as a therapy for age-associated memory impairment.
Multihormonal Control Of Melanotropin Secretion In Cold-Blooded Vertebrates
Published in Mac E. Hadley, The Melanotropic Peptides, 1988
Marie-Christine Tonon, Jean-Michel Danger, Marek Lamacz, Philippe Leroux, Saida Adjeroud, Ann C. Andersen, Kemenade Lidy Verburg-van, Bruce G. Jenks, Georges Pelletier, Lise Stoeckel, Arlette Burlet, Gotfryd Kupryszewski, Hubert Vaudry
Using the perifusion technique, GABA receptors have recently been characterized in two amphibian species. In Xenopus laevis, administration of GABA induces a dose-dependent inhibition of α-MSH release from neurointermediate lobes.165 Moreover, GABA, baclofen (a GABAB receptor agonist), and the two GABAA receptor agonists, isoguvacine, and homotaurine, inhibit α-MSH secretion from isolated Xenopus melanotrophs.169 The absence of a stimulatory phase during the onset of GABA administration165 and the fact that bicuculline, a GABAA receptor antagonist, has no effect on GABA-induced inhibition of α- MSH secretion in vitro,175 indicate that, in Xenopus, GABA acts mainly through activation of GABAB receptors. In vivo administration of GABA to Xenopus laevis causes a dose- dependent bleaching of the skin,165 a result consistent with in vitro findings in this species. In Rana ridibunda, both GABA and muscimol, a GABAA receptor agonist, cause a brief stimulation of α-MSH release followed by an inhibition (Figure 5).164 Picrotoxin, a Cl channel blocker, abolishes only the stimulatory effect of GABA, whereas bicuculline totally inhibits the effects of GABA (both stimulatory and inhibitory phases) (Figure 6). Administration of baclofen induces a dose-dependent inhibition of α-MSH secretion. In contrast to GABA and muscimol, baclofen does not cause any stimulatory effect whatever the dose.164 Thus, in amphibians, as is mammals,171,173,174 neurointermediate lobe tissue contains both GABAA and GABAB receptors.164,169 Activation of either of these receptors induces inhibition of α-MSH release.164,169 Nevertheless GABA acts essentially through GABAB receptors in Xenopus melanotrophs, whereas in Rana, the effect of GABA is mainly achieved through activation of GABAA receptors.
Lecanemab (BAN2401): an anti–beta-amyloid monoclonal antibody for the treatment of Alzheimer disease
Published in Expert Opinion on Investigational Drugs, 2023
Grace E. Vitek, Boris Decourt, Marwan N. Sabbagh
The key factor that, together with pharmacokinetic properties, appears to determine the clinical profile of each agent is the degree of Aβ oligomer selectivity [19]. Aducanumab and gantenerumab primarily target insoluble amyloid plaques, with partial oligomer selectivity [19]; donanemab selectively targets amyloid plaques, without oligomer selectivity [20]; and lecanemab is unique in its preferential target of soluble Aβ protofibrils (large oligomers) over plaques [19]. Somewhat related to this class, valiltramiprosate is an oral anti-amyloid agent with a similar target but a different mechanism; this small molecule prodrug is metabolized into tramiprosate (also known as homotaurine), which inhibits the formation and aggregation of soluble Aβ oligomers with no plaque interaction [19].