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Chemical Compound Review:

CHEMBL280450 N-methoxy-1-(1-methyl-5,6- dihydro-2H...

Synonyms: CHEBI:120601, AC1O5KIP

Schwarz, R.D. et al., Hartvig, P. et al., Rockwood, K. et al., Zheng, X.M., Callahan, M.J., et al.

Hartvig, Nordberg, Torstenson, Sjöberg, Fasth, Långström, Schwarz, Callahan, Coughenour, Dickerson, Kinsora, Lipinski, Raby, Spencer, Tecle, Jack, Slomkowski, Gracon, Hoover, Felmlee, Stewart, Xu, Shiung, O'Brien, Cha, Knopman, Petersen, Zheng,

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MILAMELINE

MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD [1].

Psychiatry related information on MILAMELINE

SETTING: Training session for a multicenter trial of milameline, a direct muscarinic agonist, in the treatment of Alzheimer's disease [2].

High impact information on MILAMELINE

Combining tacrine with milameline reverses a scopolamine-induced impairment of continuous performance in rhesus monkeys [3].
On binding, milameline stimulated phosphatidylinositol hydrolysis in hM(1) and hM(3) CHO cells and inhibited forskolin-activated cAMP accumulation in hM(2) and hM(4) CHO cells [4].
Milameline (E-1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxaldehyde, O-methyloxime monohydrochloride, CI-979, PD129409, RU35926) was characterized in vitro and evaluated for effects on central and peripheral cholinergic activity in rats and rhesus monkeys [4].
In rats, milameline decreased spontaneous and scopolamine-induced swimming activity, improved water-maze performance of animals impaired by basal forebrain lesions, increased cortical blood flow, decreased core body temperature, and increased gastrointestinal motility [4].
In muscarinic binding studies, milameline displayed nanomolar affinity with an agonist ligand and micromolar affinity with antagonist ligands, with approximately equal affinities determined at the five subtypes of human muscarinic receptors (hM(1)-hM(5)) with whole cells or membranes from stably transfected Chinese hamster ovary (CHO) cells [4].

Associations of MILAMELINE with other chemical compounds

The results suggest a possible action of milameline both on presynaptic muscarinic receptor subtypes as well as dopamine levels dependent on the receptor reserve of the muscarinic receptor subtypes [5].

Analytical, diagnostic and therapeutic context of MILAMELINE

Detecting regional cerebral blood flow changes in Alzheimer's patients after milameline treatment: activation or baseline SPECT [6]?

References

MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD. Jack, C.R., Slomkowski, M., Gracon, S., Hoover, T.M., Felmlee, J.P., Stewart, K., Xu, Y., Shiung, M., O'Brien, P.C., Cha, R., Knopman, D., Petersen, R.C. Neurology (2003) [Pubmed]
Interrater reliability of the Clinical Dementia Rating in a multicenter trial. Rockwood, K., Strang, D., MacKnight, C., Downer, R., Morris, J.C. Journal of the American Geriatrics Society. (2000) [Pubmed]
Combining tacrine with milameline reverses a scopolamine-induced impairment of continuous performance in rhesus monkeys. Callahan, M.J. Psychopharmacology (Berl.) (1999) [Pubmed]
Milameline (CI-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization. Schwarz, R.D., Callahan, M.J., Coughenour, L.L., Dickerson, M.R., Kinsora, J.J., Lipinski, W.J., Raby, C.A., Spencer, C.J., Tecle, H. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography. Hartvig, P., Nordberg, A., Torstenson, R., Sjöberg, P., Fasth, K.J., Långström, B. Dementia and geriatric cognitive disorders. (2002) [Pubmed]
Detecting regional cerebral blood flow changes in Alzheimer's patients after milameline treatment: activation or baseline SPECT? Zheng, X.M. Journal of nuclear medicine technology. (2002) [Pubmed]

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