In regards to idebenone as a nootropic:
Idebenone treatment fails to slow cognitive decline in Alzheimer's disease.
Thal LJ, Grundman M, Berg J, Ernstrom K, Margolin R, Pfeiffer E, Weiner MF, Zamrini E, Thomas RG.
Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093-0624, USA. lthal@ucsd.edu
OBJECTIVE: To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD). METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were over age 50 with a diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores between 12 and 25. Subjects were treated with idebenone 120, 240, or 360 mg tid, each of which was compared with placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog) and a Clinical Global Impression of Change (CGIC). Secondary outcome measures included measurements of activities of daily living, the Behavioral Pathology in Alzheimer's Disease Rating Scale, and the MMSE. RESULTS: Five hundred thirty-six subjects were enrolled and randomized to the four groups. Except for a slight difference in age, there were no differences in patient characteristics at baseline. For the primary outcome measures, there were no significant overall differences between the treatment groups in the prespecified four-group design. In an exploratory two-group analysis comparing all three treated groups combined with placebo, drug-treated patients performed better on the ADAS-Cog in both the intent-to-treat (ITT) and completers analyses. There were no differences in the CGIC scores for the ITT or completers analyses in either the four-group or the two-group analyses. There were no overall differences on any of the secondary outcome measures in any of the analyses. CONCLUSION: Idebenone failed to slow cognitive decline in AD that was of sufficient magnitude to be clinically significant.
Publication Types:
* Clinical Trial
* Multicenter Study
* Randomized Controlled Trial
PMID: 14663031 [PubMed - indexed for MEDLINE]
Here is a useful summary on idebenone
Coenzyme Q10 and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits
Vanna Geromel, Niklas Darin, Dominique Chrétien, Paule Bénit, Pascale DeLonlay, Agnès Rötig, Arnold Munnich and Pierre RustinCorresponding Author Contact Information, E-mail The Corresponding Author
Service de Génétique Médicale and Unité de Recherches sur les Handicaps Génétiques de l’Enfant INSERM U-393, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743, Paris Cedex 15, France
Received 14 May 2002; revised 29 July 2002; accepted 29 July 2002. ; Available online 16 September 2002.
Idebenone (6-(10-hydroxydecyl)2,3-dimethoxy-5-methyl-1,4-benzoquinone) is a synthetic compound, initially patented by Takeda Chemical Industries, Osaka, Japan, which various properties were extensively reviewed by Nagy in 1990. The drug was introduced to the Japanese market as early as 1986. Initially its main indication was age-dependent impairments of brain functions. Its redox properties are those of a quinone analogue, with possible pro- and antioxidant activities, and ability to interact with other redox carriers including CoQ10 itself in the mitochondrial respiratory chain. In rodents, intraperitoneal LD50 was estimated to be about 800 mg/kg body weight while it would exceed 10 g/kg for subcutaneous and oral administration. Reversible subacute toxicity in rodents was observed for 2,5 g/kg/d, while 500 mg/kg/d provoked diarrhea in beagle dogs. Chronic toxicity study in the beagle dog resulted in similar figures with first signs appearing at 500 mg/kg body weight doses per os. Idebenone was found to be neither immunogenic in rodents nor mutagenic in bacteria or mice. In human, idebenone is absorbed rapidly and circulating concentration increases in a dose-dependent manner (2 μM 2 h, after 100 mg oral supplementation), but rapidly tends to lower by excretion.
In human, the safety of idebenone (60–300 mg) was established on a long-term period by treating elderly patients for two years without remarkable side effects [25]. However, idebenone, as other quinone analogues, is a redox active compound with distinctive kinetics properties towards other redox carriers, including components of the respiratory chain complexes. In vitro, it is able to favorably compete with natural CoQ10 to mediate electron transfer in isolated mitochondria and to divert a variable part of the electrons at the expense of electron flow to oxygen, particularly from complex I [26]. Being thus readily reduced, idebenone revealed then as a powerful antioxidant at the surface of the mitochondrial inner membrane.
Regarding the structural features of ubiquinone (coenzyme Q10) and idebenone. Unfortunately I could not attach a picture of the 2 compounds
Taking into account the extended dimension of CoQ10, it appears that the molecule is too long to fit the hydrophobic domain of a phospholipid bilayer, except if folded. Notice the short side-chain of idebenone (10 carbons) as compared to CoQ10 (50 carbons), the saturation of the idebenone side-chain, the presence of a terminal hydroxyl group, and of dimethoxy and methyl residues on the benzoquinone ring. All this concurs to make idebenone less hydrophobic than coenzyme Q10, affecting its partition and diffusion in biological membranes.
