Table 1

Biological activities of ryanodine and related compounds

Scheme Number	Compound	Skeletal IC₅₀ nm	Cardiac IC₅₀ nm	Skeletal K_D nm	Cardiac K_D nm	Fractional Conductance
1	ryanodine	10^1-a	2.8^bm	7^1-k	2.5^bo	56.8^1-c
2	ryanodol	35,000^1-a	1725^bm	12000^1-k	1556^bo	69.4^1-c
2C	10-O-aminoacetyl-ryanodol		140^1-f		346^1-b
4	anhydroryanodine	10,000^1-a		2900^1-k
44	10-O-pyrrole-carbonyl-ryanodol		227^bm	52^1-p	13°	52.2^1-c
50	3-epiryanodine		178^bm	350^1-p	178^bo	42.9^1-c
55	9,12-didehydroryanodine	13^1-a	3.9^bm	7^1-k	2.5^bo	58.3^1-c
57	9α-hydroxyryanodine			110^1-k
60	19-hydroxyryanodine	88^1-a
61	ester B			240^1-k
62	ester C₁	500^1-d		210^1-k
63	3-O-nicotinoyl-ryanodol	1429^1-d	446^bm	1100^1-k	337^1-b
65	ester A	37.04^1-d		110^1-k	61^1-o	61.5^1-c
66	ester D	90.91^1-d		51^1-k
67	ester E	>2000^1-d
68	ester F	556^1-d
70	anhydroester A			5200^1-k
71	9-hydroxy-anhydroryanodine	667^1-d		2600^1-k
72	N-butyl-ryanodine	880^1-a
73	N-benzyl-ryanodine	310^1-a
74	N,15-O-dimethyl-ryanodine	280^1-a
75	N,4-O,15-O-trimethyl-ryanodine	4500^1-a
76	N,6,O,15-O-trimethyl-ryanodine	1300^1-a
77	N,4-O,10-O,15-O-tetramethyl-ryanodine	>10,000^1-a
78	10-acetyl-ryanodine	140^1-a
79	10-O-(NCBZ-aminoacetyl)-ryanodine	4.2^1-e	62^bm	1.4^1-e	29^1-o	29.4^1-c
80	10-O-(NCBZ-3-aminopropanoyl)-ryanodine	6.4^1-e		2.2^1-e
81	10-O-(N,N′-bis-CBZ-3-guanidinopropanoyl)-ryanodine	51.8^1-e		20.4^1-e
82	10-O-(N,N′-bis-CBZ-2-guanidinoacetate)-ryanodine	33.2^1-e		12.9^1-e
83	10-O-(2-aminoacetyl)-ryanodine	2.0^1-e		0.5^1-e
84A	10-O-(3-aminopropanoyl)-ryanodine	1.5^1-e	14.2^bm	0.5^1-e	0.61^1-o	14.3^1-e
84B	10-O-(3-[4-azidobenzamido]-propanoyl)-ryanodine	3.2^1-f
84C	10-O-(3-[2-nitro-5-azidobenzamido]-propanoyl)-ryanodine	36.6^1-e		21.6^1-e
84D	10-O-(3-[4-benzoylbenzamido]-propanoyl)-ryanodine	6.0^1-f
85	10-O-(2-guanidinoacetyl)-ryanodine	1.3^1-e		0.4^1-e
86	10-O-(guanidinopropanoyl)-ryanodine	1.4^1-e	0.6^bm	0.3^1-e	0.55^bo	5.8^1-c
87	10-O-(hemisuccinyl)-ryanodine	>1000^1-g
88	10-O-(N-methylsuccinamidyl)-ryanodine	49.4^1-g
90	10-oxoryanodine	11.67^1-h
92	4,12-seco-4,12-dioxoryanodine	750^1-i
93	4,12-seco-4,12-dihydroryanodine	255^1-i
94	4,12-hemiketal-4-hydroxyryanodine	19.35^1-i
95	4,12-hemiketal-4-hydroxy-12-hydroxyamino-ryanodine	133^1-i
97	4,12-hemiketal-4-hydroxy-12-phenylhydrazino-ryanodine	461^1-i
98	4,12-hemiketal-4-hydroxy-12-phenylazo-ryanodine	255^1-i
99	4,12-hemiketal-4-hydroxy-12-semicarbazino-ryanodine	196^1-i
100	4,12-hemiketal-12-hydroxyryanodine	42.85^1-i
101	4,12-hemiketal-4-hydroxyamino-12-hydroxyryanodine	85.17^1-i
102	4,12-hemiketal-4-methoxyamino-12-hydroxyryanodine	52.17^1-i
103	4,12-hemiketal-4-benzyloxyamino-12-hydroxyryanodine	92.31^1-i
104	4,12-hemiketal-4-hydrazino-12-hydroxyryanodine	109^1-i
105	4,12-hemiketal-4-benzoylhydrazino-12-hydroxyryanodine	200^1-j
106	4,12-hemiketal-4-phenylhydrazino-12-hydroxyryanodine	222^1-i
107	4,12-hemiketal-4-semicarbazino-12-hydroxyryanodine	120^1-i
108	4,12-seco-4-oxo-12-hydroxyimino-ryanodine	705^1-i
109	4,12-seco-4-hydroxyimino-12-oxo-ryanodine	1579^1-i
110	4,12-seco-4-methoxyimino-12-oxo-ryanodine	1600^1-i
111	4,12-seco-4-benzyloxyimino-12-oxo-ryanodine	923^1-i
114A	21-(2-hydroxyethylmercapto)-ryanodine	>1200^1-j
114C	21-(2-[3,3,3-trifluoro-2-diazo-propanoyloxy]ethylmercapto)-ryanodine	4^1-f
114D	21-(4-hydroxybutylmercapto)-ryanodine	25^1-f
114E	21-(4-[4-azidobenzoyloxy]-butylmercapto)-ryanodine	198^1-f
115	21-(propylmercapto)-ryanodine	>1200^1-j
116	21-(t-butylmercapto)-ryanodine	>1200^1-j
117	9-epiryanodine	41^1-a		13^1-k
118	8,9-didehydro-10-oxoryanodine	29.17^1-h
119+120	9,21-epoxy-ryanodine	140^1-a	60^bm		30^1-b
120	9β,21β-epoxy-ryanodine	29.17^1-k				56.8^1-c
121A	9,21-dihydroxyryanodine	4900^1-a		36^1-k
122	21-azido-9α-hydroxyryanodine		52^bm	78^1-k	25^1-b	56.3^1-c
124	21-p-nitro-benzamido-ryanodine		14.1^bm	22^1-k	19^1-b	26.1^1-c
125	21-bodipy-ryanodine			13^1-k
126	8,9-didehydroryanodine	13.46^1-h	6.67^hn
131	8β-amino-9α-hydroxyryanodine		407^km	760^1-k	322^1-b
132	8α-amino-9β-hydroxyryanodine			3880^1-k
136	4,6-borate-dehydroryanodine	3.5^1-l	4.19^ln
137	4,6-methylboronate-dehydroryanodine	15.91^1-l	3.75^ln
138	4,6-phenylboronate-dehydroryanodine	7.45^1-l
139	4,6-cyclohexylboronate-dehydroryanodine	4.93^1-l
140	4,6-(3-thienyl)boronate-dehydryanodine	3.88^1-l	2.61^ln
142	10,12-methylphosphonate-dehydroryanodine	83.33^1-l
144	10,12-N-methylphosphoramidate	77.78^1-l		<51^1-l
148	2-deoxy-2(13)-dehydroryanodine	26.92^1-l	5.81^ln
149α	2-deoxy-2,13α-epoxyryanodine	250^1-l	225^ln
149β	2-deoxy-2,13β-epoxyryanodine	49.30^1-l	22.78^ln
150	13-hydroxyryanodine	175^1-l	45^ln
151	10-hydroxyiminoryanodine	13.46^1-h
153	10-epiryanodine	3.6^1-h	2.31^hn
154	10-epi-amino-ryanodine	5.14^1-h
155	10-epi-benzamido-ryanodine	36.84^1-h
156	10-epi-hydroxyamino-ryanodine	10.61^1-h
158	10-epi-methoxyamino-ryanodine	5.14^1-h	5.0^hn
162	10-epi-(4-azidobenzoyl)hydrazido-ryanodine	5.22^1-h
163	21-nor-9-oxoryanodine	35.0^1-h	27.69^hn
164	21-nor-9_ax-hydroxyryanodine	564.5^1-h	66.66^hn
167	21-nor-10-deoxyryanodine	53.85^1-h
168	10-deoxydehydroryanodine	9.46^1-h	4^hn
170	21-nor-10-deoxy-9_ax-hydroxyryanodine	1750^1-h	429^hn
171	lactam	8.33^1-h	24.32^hn

Skeletal muscle IC₅₀, and skeletal and cardiac muscleK_D values were measured in rabbit tissues. IC₅₀ for skeletal muscle calculated using competitive displacement of ryanodine by the ryanoid being tested. IC₅₀for cardiac muscle represents the concentration of the ryanoid that produced a 50% increase in the calcium permeability of SR membranes measured using the method of Fleischer et al. (1985). Fractional cond., Fractional conductance is the ratio of the chord conductance at +60 mV before and after modification of the sheep cardiac RyR reconstituted into a planar lipid bilayer. IC₅₀, concentration that inhibits 50%.
↵1-a Waterhouse et al., 1987.
↵1-b Mitchell et al., 1996.
↵1-c Tinker et al., 1996.
↵1-d Jefferies et al., 1992b.
↵1-e Bidasee et al., 1995.
↵1-f Kahl et al., 1994.
↵1-g Gerzon et al., 1993.
↵1-h Jefferies et al., 1996b.
↵1-i Jefferies et al., 1993.
↵1-j Jefferies and Casida, 1994.
↵1-k Welch et al., 1994.
↵1-l Jefferies et al., 1996a.
1-m IC₅₀ was measured using porcine cardiac muscle.
1-n IC₅₀ was measured in canine cardiac muscle.
↵1-o Welch et al., 1997.
↵1-p Welch et al., 1996.