. Author manuscript; available in PMC: 2015 Oct 1.

Published in final edited form as: Bioorg Med Chem Lett. 2014 Jul 29;24(19):4754–4758. doi: 10.1016/j.bmcl.2014.07.062

Table 1.

Comparison of the DAT, SERT, and NET-mediated Release Activity and 5-HT_2A Receptor Activity of Substituted Tryptamines


					EC₅₀, (nM)^a			5-HT_2A^b

PAL	#	Substituent	R	R’	DA	5HT	NE	EC₅₀, (nM)	E_MAX, (%)
287	1	-	-	-	12.6 ± 0.4^c	3.4 ± 0.2 ^c	11.1 ± 0.9 ^c	-	-
235	4a	-	H	H	164 ± 16	32.6 ± 2.6	716 ± 46	7.36 ± 0.56	104 ± 4
152	4b	-	Me	H	321 ± 23	22.4 ± 1.4	733 ± 94	50.7 ± 7.1	96 ± 2
536	4c	-	Et	H	6660 ± 551^d	18.6 ± 1.6	3862 ± 635^d	38.3 ± 2.7	99 ± 2
637	4d	1-Me	H	H	>10,000	53.1 ± 4.9	>10,000	209 ± 40	99 ± 3
551	4e	4-F	H	H	106 ± 5	108 ± 9	1123 ± 211	28.1 ± 8.4	108 ± 3
548	4f	4-OMe	H	H	>10,000	4114 ± 261^d	>10,000	9.02 ± 0.65	108 ± 2
22	4g	5-Me	H	H	>10,000	139 ± 19	>10,000	6.00 ± 1.1	100 ± 2
441	4h	5-Cl	H	H	476 ± 34	19.1 ± 2.9	>10,000	4.11 ± 0.59	109 ± 3
518	4i	5-Br	H	H	478 ± 25	75.0 ± 7.7	>10,000	5.14 ± 0.90	108 ± 1
284	4j	5-F	H	H	82.3 ± 6.8	10.1 ± 0.9	464 ± 46	2.64 ± 0.36	110 ± 2
234	4k	5-OMe	H	H	11031 ± 580	2169 ± 259	>10,000	0.503 ± 0.09	119 ± 2
227	41	6-F	H	H	106 ± 4	4.4 ± 0.4	1575 ± 104	4.56 ± 0.28	101 ± 2
263	4m	6-OMe	H	H	113 ± 8	53.8 ± 5.4	465 ± 45	2443 ± 491	111 ± 5
522	4n	6-Me	H	H	353 ± 13	51.6 ± 5.8	>10,000	75.3 ± 10	110 ± 4
286	4o	7-Me	H	H	3380 ± 220	23.7 ± 1.9	>10,000	44.7 ± 5.7	103 ± 3
532	4p	7-Cl	H	H	1330 ± 61	8.03 ± 1.3	656 ± 60	18.8 ± 4.0	102 ± 2
533	4q	7-OMe	H	H	2118 ± 88	44.6 ± 3.8	5600 ± 815	496 ± 50	107 ± 3
17	7a	-	H	Me	78.6 ± 4.0	21.7 ± 1.0	112 ± 6	23.1 ± 2.4	103 ± 3
542	7b	5-Cl	H	Me	54.3 ± 1.8	16.2 ± 2.2	3434 ± 516	6.27 ± 1.3	105 ± 1
212	7c	5-F	H	Me	37.0 ± 2	14 ± 1	78 ± 5	8.47 ± 1.9	107 ± 3
125	7d	-	H	Et	232 ± 17	23.2 ± 1.7	640 ± 76^e	>10,000	21 ± 11
640	(-)-7d	-	H	(R)-Et	654 ± 50	54.9 ± 7.8	3670 ± 1190^e	Inactive at 10 μM
647	(+)-7d	-	H	(S)-Et	57.6 ± 3.1	34.7 ± 4.9	592 ± 97^e	1250 ± 310	61 ± 8
526	7e	5-Cl	H	Et	1838 ± 150^d	33.2 ± 3.6	>10,000	249 ± 22	87 ± 1
545	7f	5-F	H	Et	150 ± 7	36.6 ± 3.2	5334 ± 970	246 ± 46	87 ± 3

Release EC₅₀ values are reported as means ± SD and are the result of N=3 performed in triplicate.

Calcium mobilization EC₅₀ and E_MAX values are reported as means ± SEM and are the result of three independent experiments performed in duplicate.

Release data²²

Value is IC₅₀ for uptake inhibition in nM.

7d, (-)-7d, and (+)-7d were partial releasers of NE with Emax values of 78%, 75% and 71% respectively.