Table 1.

Pharmacological properties of selected acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease

Properties	Tacrine	Donepezil	Rivastigmine	Galantamine
Class	Aminoacridine	Piperidine	Carbamate	Tertiary alkaloid
AChE inhibition	Reversible Noncompetitive	Reversible Noncompetitive	Pseudo-irreversible Noncompetitive	Reversible Competitive
Dose (mg/day)	80–160	5–10	6–12	16–24
Duration	Short-acting	Short-acting	Intermediate-acting	Short-acting
Brain AChE selectivity IC50 (nmol/L)	125	33	42,000	3,900
Serum BuChE selectivity IC50 (nmol/L)	7.2	988	54,000	18,600
BuChE/AChE selectivity	0.06	30	1.3	4.8
Cmax (μg/L)	5.1 (10 mg) 20.7 (20 mg) 33.9 (30 mg)	7.2 (5 mg) 25.6 (10 mg)	5.07 (2 mg × 2) 14.1 (6 mg × 2)	42 (12 mg × 2) 137 (16 mg × 2)
Tmax (h)	1–2	3–5	0.5–2	0.9–2
AUC (μg/L/h)	2–4	539	15.4 (3 mg × 2) 55.9 (6 mg × 2)	1.1
T1/2 (h)	1.3	50–80	0.6–2	7–8
Bioavailability (%)	17–37	100	35–40	100
Protein binding (%)	55	96	40	18
Clearance (L/h/kg)	2.42	0.13	1.5 (6 mg bid)	0.34
Vd (L/kg)	3.5–7	14	1.8–2.7	2.64
Cytochrome P450	CYP1A2	CYP2D6	Carbomoylation	CYP2D6
Metabolism	CYP2D6	CYP3A4		CYP3A4
Active metabolites	1-hydroxy-tacrine	6-O-desmethyldonepezil	NAP 226–90	Sanguinine
Urine excretion (%)	<3	17	Metabolite	50
Efficacy	4.0–5.3 vs 0.8–2.8	2.8–4.6 vs 0.7–1.2	1.9–4.9 vs 0.7–1.2	3.1–3.9 vs 1.73
ADAS-Cog vs Placebo
Adverse effects
Nausea	3+	3+	3+	2+
Vomiting	2+	2+	2+	2+
Diarrhea	2+	2+	2+	1+
Dizziness	2+	1+	2+	1+
Headache	1+	0	1+	0
Abdominal pain	1+	0	1+	0
Anorexia	2+	1+	1+	0
Bradycardia	0	0	0	0
Fatigue	0	1+	1+	1+
Muscle clamps	0	1+	0	0
Agitation	2+	1+	0	1+
Dyscrasia	0	0	0	0
Liver dysfunction	3+	0	0	0

Sources: Cacabelos, CIBE Database, 2005; Cacabelos 2005a, ^b; Bentué-Ferrer et al 2003; Giacobini 2000, ²⁰⁰⁶.