Tacrine

spinqualitylabelsall models Tacrine, also known as Cognex Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Better Known as: Cognex

• Marketed By: Parke Davis Pharmaceuticals
  
• Major Indication: Alzheimer's Disease
  
• Drug Class: Acetylcholinesterase Inhibitor
• Date of FDA Approval (Patent Expiration): 1993 (N/A)
  
• 1994 Sales: $100 Million
• Importance: One of the the first treatments for the symptoms of Alzheimer's Disease, although no definitive proof exists as to whether it alters the progression of the disease.
• See: Pharmaceutical Drugs for more information about other drugs and disorders

Mechanism of Action

Tacrine is an Acetylcholinesterase (AChE) inhibitor. It binds to the active site of AChE, utilizing many of the same residues which bind and break down acetylcholine. By inhibiting AChE, the important neurotransmitter, acetylcholine, is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in Alzheimer's Disease patients. Tacrine primarily interacts with residues Phe 330, His 440, Trp 84, & Ser 200 in tightly binding to the AChE binding site via pi stacking interactions. It is clearly visible how Tacrine interferes with the binding of acetylcholine, outcompeting acetylcholine for nearly the same space in the active site.

Pharmacokinetics

Acetylcholinesterase Inhibitor Pharmacokinetics Parameter Donepezil Tacrine Rivastigmine Galantamine Tmax (hr) 3.6 1.5 .3 1.2 Cmax (ng/ml) 6.5 15.7 29.3 42.6 Bioavailability (%) 100 17 36 100 Protein Binding (%) 96 55 40 10 T1/2 (hr) 70 3 5 7.3 AUC (ng/ml/hr) 380 80.4 191 427 IC50 (nM) 6.7 (Rat) 450 (Human) 1535 (Human) 1995 (Rat) Dosage (mg) 5 160 6 8 Metabolism Hepatic (CYP2D6 & CYP3A4) & AChE Hepatic (CYP1A2) & AChE AChE Hepatic (CYP3A4 & CYP2D6) & AChE For Pharmacokinetic Data References, see: References

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