Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites.
In an attempt to define pharmacophoric differences between 5-HT1, 5-HT1A and 5-HT2 recognition sites, a number of rigid analogs were studied and compared to analogous free chain tryptamines. Racemic partial ergolines RU 27849 and RU 28306 showed reduced potency at all 5-HT1 sites, but were at least equipotent to analogous tryptamines at the 5-HT2 site. A nonergoline-like constrained analog of tryptamine was similar in potency to RU 27849 at all 5-HT1 sites, but showed a 4-fold enhancement in potency over RU 27849 and tryptamine at the 5-HT2 site. At all 3 sites, 3-(tetrahydropyridyl) indoles (unless substituted at the indole 2-position) were the most potent rigid analogs studied and represent the most promising class for the development of selective compounds.
Taylor
E W
EW
Dept. of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721.
Nikam
S
S
Weck
B
B
Martin
A
A
Nelson
D
D
D000818:Animals; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007211:Indoles / Q000378:metabolism; D008297:Male; D008433:Mathematics; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000378:metabolism*
D007211:Indoles; D011985:Receptors, Serotonin; D014363:Tryptamines; C053845:3-aminomethyl-1,3,4,5-tetrahydrobenz(cd)indole; C053844:RU 28306; C053842:RU 27849