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Chemical Compound Review:

AC1NSMED 3-[2-[4-(4- fluorophenyl)carbonyl-1...

Synonyms: MOLI000115, MOLI001676, [18F]Altanserin

Pinborg, L.H. et al., Frank, G.K. et al., Smith, G.S. et al., Meltzer, C.C. et al., Meltzer, C.C. et al., et al.

Meltzer, Smith, Price, Reynolds, Mathis, Greer, Lopresti, Mintun, Pollock, Ben-Eliezer, Cantwell, Kaye, DeKosky, Meltzer, Price, Mathis, Greer, Cantwell, Houck, Mulsant, Ben-Eliezer, Lopresti, DeKosky, Reynolds, Pinborg, Adams, Yndgaard, Hasselbalch, Holm, Kristiansen, Paulson, Knudsen, Smith, Price, Lopresti, Huang, Simpson, Holt, Mason, Meltzer, Sweet, Nichols, Sashin, Mathis, Tan, Baldwin, Van Dyck, Al-Tikriti, Roth, Khan, Charney, Innis,

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Psychiatry related information on MOLI001676

RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group [1].

High impact information on MOLI001676

The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin [2].
Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography [3].
[18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration [2].
The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed [2].
RESULTS: REC AN women had significantly reduced [18F]altanserin binding relative to CW in mesial temporal (amygdala and hippocampus), as well as cingulate cortical regions [4].

Biological context of MOLI001676

METHODS: To avoid the confounding effects of malnutrition, we studied 16 women recovered from AN (REC AN, >1 year normal weight, regular menstrual cycles, no bingeing or purging) compared with 23 healthy control women (CW) using [18F]altanserin, a specific 5-HT2A receptor antagonist on PET imaging [4].
We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site [5].
[18F]Altanserinol was obtained by NaBH4 reduction of [18F]altanserin, followed by acid hydrolysis [6].

Anatomical context of MOLI001676

For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum [7].
Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier [7].
Furthermore, we have found a trend towards loss of 5-HT(2A) receptors in the hippocampus using positron emission tomography (PET) to detect regional changes in [18F]altanserin binding [8].
The highest [18F]altanserin uptake is found in the cerebral cortex, with specific-to-nonspecific binding ratios varying from 0.53 to 1.91 in humans between 24 and 48 years of age [9].

Associations of MOLI001676 with other chemical compounds

Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls [10].

Analytical, diagnostic and therapeutic context of MOLI001676

After purification by preparative HPLC, [18F]altanserin was produced in less than 2 hr with a radiochemical yield of 10% (EOS) and a specific activity of 0.8-1.3 Ci/mumol [11].
Dynamic PET studies were carried out in 12 healthy volunteers after intravenous injection of 0.1 mCi/kg [18F]altanserin [12].

References

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Meltzer, C.C., Price, J.C., Mathis, C.A., Greer, P.J., Cantwell, M.N., Houck, P.R., Mulsant, B.H., Ben-Eliezer, D., Lopresti, B., DeKosky, S.T., Reynolds, C.F. The American journal of psychiatry. (1999) [Pubmed]
[18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge. Pinborg, L.H., Adams, K.H., Yndgaard, S., Hasselbalch, S.G., Holm, S., Kristiansen, H., Paulson, O.B., Knudsen, G.M. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography. Mintun, M.A., Sheline, Y.I., Moerlein, S.M., Vlassenko, A.G., Huang, Y., Snyder, A.Z. Biol. Psychiatry (2004) [Pubmed]
Reduced 5-HT2A receptor binding after recovery from anorexia nervosa. Frank, G.K., Kaye, W.H., Meltzer, C.C., Price, J.C., Greer, P., McConaha, C., Skovira, K. Biol. Psychiatry (2002) [Pubmed]
Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction. Meltzer, C.C., Smith, G., Price, J.C., Reynolds, C.F., Mathis, C.A., Greer, P., Lopresti, B., Mintun, M.A., Pollock, B.G., Ben-Eliezer, D., Cantwell, M.N., Kaye, W., DeKosky, S.T. Brain Res. (1998) [Pubmed]
Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent. Tan, P.Z., Baldwin, R.M., Van Dyck, C.H., Al-Tikriti, M., Roth, B., Khan, N., Charney, D.S., Innis, R.B. Nucl. Med. Biol. (1999) [Pubmed]
Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. Smith, G.S., Price, J.C., Lopresti, B.J., Huang, Y., Simpson, N., Holt, D., Mason, N.S., Meltzer, C.C., Sweet, R.A., Nichols, T., Sashin, D., Mathis, C.A. Synapse (1998) [Pubmed]
The hippocampus and depression. Sheline, Y.I., Mittler, B.L., Mintun, M.A. Eur. Psychiatry (2002) [Pubmed]
Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging. Rosier, A., Dupont, P., Peuskens, J., Bormans, G., Vandenberghe, R., Maes, M., de Groot, T., Schiepers, C., Verbruggen, A., Mortelmans, L. Psychiatry research. (1996) [Pubmed]
Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls. Sadzot, B., Lemaire, C., Maquet, P., Salmon, E., Plenevaux, A., Degueldre, C., Hermanne, J.P., Guillaume, M., Cantineau, R., Comar, D. J. Cereb. Blood Flow Metab. (1995) [Pubmed]
Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. Lemaire, C., Cantineau, R., Guillaume, M., Plenevaux, A., Christiaens, L. J. Nucl. Med. (1991) [Pubmed]
Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography. Biver, F., Goldman, S., Luxen, A., Monclus, M., Forestini, M., Mendlewicz, J., Lotstra, F. European journal of nuclear medicine. (1994) [Pubmed]

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