Tacrine

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Tacrine, also known as Cognex

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 , utilizing many of the same residues which . 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 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 with the binding of acetylcholine, outcompeting acetylcholine for nearly the same space in the active site. [1]

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

References

  1. Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9031-5. PMID:8415649


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