Disease relevance of Alvameline

• Furthermore, Lu 25-109 did not attenuate the reflex mechanisms restoring blood pressure following orthostasis in cats [1].
• Unlike non-selective muscarinic agonists and acetylcholinesterase inhibitors, Lu 25-109 did not induce hypothermia, tremor or salivation in mice [1].

Psychiatry related information on Alvameline

• Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group [2].

High impact information on Alvameline

• Lu 25-109 [5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1-methylpyridine] , has M agonistic and M2/M3 antagonistic effects at muscarinic receptors in vitro; a pharmacological profile that may be beneficial in treatment of Alzheimer's disease [1].
• In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro [1].
• Lu 25-109 had no effect on mean blood pressure in anaesthetized rats [1].
• Lu 25-109 and O-Me-THPO produced a significant increase in heart rate [1].
• Radioligand binding experiments demonstrated a small difference in affinity for Lu 25-109 in the parotid gland compared with the bladder, the pKi values being 6.2+/-0.1 versus 6.5+/-0.1 (n=4) [3].

Biological context of Alvameline

• Biotransformation of the M1-muscarinic agonist Lu 25-109 (5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine) , in development for the treatment of Alzheimer's disease, was investigated to obtain information on the identity of human hepatic cytochrome P-450 enzymes involved in its metabolism [4].
• This double-blind, placebo-controlled, two-part, inpatient bridging study was designed to evaluate the safety and tolerability of multiple oral doses of Lu 25-109 in patients with Alzheimer's Disease(AD), and to determine the maximum tolerated dose (MTD) in this population [5].

Anatomical context of Alvameline

• PURPOSE: To investigate the blood-brain barrier (BBB) passage of the M1 muscarine agonist Lu 25-109 (5-(2-Ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-methylpyridine) and potential metabolites using in vivo microdialysis [6].
• 5. The metabolite production in human liver microsomes was NADPH-dependent, suggesting that the metabolism of Lu 25-109 in human liver microsomes is primarily P-450-dependent [4].

Associations of Alvameline with other chemical compounds

• The aim of this study was to evaluate the effects of a novel antimuscarinic agent, Lu 25-109, a partial M1 receptor agonist, and M2/M3 receptor antagonist in human and pig detrusor to establish its affinity for muscarinic receptors in human detrusor and parotid gland and to compare the results with those obtained with oxybutynin [3].
• To examine the effects of the combined muscarinic ml-agonist/m2-antagonist Lu 25-109 on regulated processing of the amyloid protein precursor (APP), we used both transfected cells expressing human muscarinic m1 or m2 acetylcholine receptors, and fresh rat hippocampal slices [7].

Gene context of Alvameline

• Both responses appeared to reflect post-translational mechanisms because levels of APP message were unchanged after 60 minutes of stimulation with Lu 25-109 [7].
• In as much as stimulation of APPs secretion is associated with reduced formation of A beta peptides, Lu 25-109 may be useful to reduce A beta generation, and thus, slow amyloid plaque formation [7].
• One metabolite, Lu 32-181 (N-oxide), could be reduced back to Lu 25-109, a reaction not inhibited by the applied cytochrome P-450 inhibitors [4].

Analytical, diagnostic and therapeutic context of Alvameline

• In the present study, we compare functional in vivo effects of Lu 25-109 and reference compounds in animal models of muscarinic cholinergic function [1].
• Thus, the titration regimen employed did not improve the overall tolerability of Lu 25-109 [5].

References