Galantamine

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Galantamine, also known as Razadyne

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Better Known as: Razadyne

  • Marketed By: Ortho Mcneil Janssen Pharmaceuticals (Subsidiary of Johnson & Johnson)
  • Major Indication: Alzheimer's Disease
  • Drug Class: Acetylcholinesterase Inhibitor
  • Date of FDA Approval (Patent Expiration): 2001 (2008)
  • 2006 Sales: $225 Million[1]
  • Importance: Part of a newer generation of treatments for 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

Galantamine is a potent Acetylcholinesterase (AChE) inhibitor to the active site of . 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. Galantamine binds to the same active site gorge as acetylcholine Glu 199, Phe 330, Trp 84, His 440, Phe 288, PHe 290, Tyr 121, Phe 331, Gly 119, Ser 200, Gly 118, and Gly 117 to tightly bind to AChE.[2] These interactions, which are primarily hydrophobic and pi stacking interactions, allow Galantamine outcompete Acetylcholine for the AChE 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

References

  1. ↑ Irena Melnikova, Therapies for Alzheimer's disease, Nature Reviews Drug Discovery 6, 341-342 (May 2007)
  2. ↑ Greenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc. 2004 Dec 1;126(47):15405-11. PMID:15563167 doi:http://dx.doi.org/10.1021/ja0466154


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