TABLE 1

FLAP predictions, MetaSite predictions, and reported site of metabolism in CYP2D6 for the literature data set

	pKa^a	FLAP^b
N-Dealkylated by CYP2D6
Dexfenfluramine	9.59			(Gross et al., 1996)
Hydromorphone^f	8.52			(Benetton et al., 2004)
Morphine^f	8.35			(Projean et al., 2003)
Chlorpheniramine	9.05			(Fried et al., 2002)
Eletriptan^e^,^f	9.29			(Evans et al., 2003)
Not N-dealkylated by CYP2D6
Doxepin	8.93			(Haritos et al., 2000)
Methylenedioxymethamphetamine	9.65			(Lin et al., 1997)
Chlorpromazine	9.24			(Yoshii et al., 2000)
Perhexiline	10.32			(Sorensen et al., 2003)
N-Butyl amphetamine	10.09			(Bach et al., 1999)
Ethylamphetamine	9.99			(Bach et al., 1999)
4-Methoxy-ethylamphetamine	9.99			(Bach et al., 1999)
Brofaromine^e	9.55			(Feifel et al., 1993)
Buflomedil^e	9.48			(Kanmacher et al., 2000)
Mequitazine	9.36			(Nakamura et al., 1998)
Carteolol^e	9.34			(Kudo et al., 1997)
Tolperisone^e	9.27			(Dalmadi et al., 2003)
Bufuralol^e	8.92			(Narimatsu et al., 2002)
Ibogaine^e	8.81			(Obach et al., 1998)
Propafenone^e	9.13			(Kroemer et al., 1989)
Tropisetron	9.16			(Fischer et al., 1994)
Bunitrolol^e	9.34			(Narimatsu et al., 1994)
Bisoprolol	9.24	Compound not aligned	(Horikiri et al., 1998)

↵ a Predicted pKa values from MOKA.
↵ b Encircled are the parts of the molecules aligned with site of metabolism in DXM/tropisetron from the FLAP alignment.
↵ c Encircled are the parts of the molecules comprising the top two ranked sites of metabolism from MetaSite.
↵ d Encircled is the site of metabolism in CYP2D6 reported in the literature.
↵ e FLAP alignment with tropisetron.
↵ f Protonation of the nitrogen results in a stereogenic center. The MetaSite predictions comprise both the R and S stereoisomers.