N,N-di-n-propylserotonin: binding at serotonin binding sites and a comparison with 8-hydroxy-2-(di-n-propylamino)tetralin.
8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a serotonergic agonist with high affinity and selectivity for a particular population of central serotonin (5-HT) binding sites (i.e., 5-HT1A sites). Because the selectivity of 8-OH-DPAT may be due to the terminal amine substituents, the di-n-propyl analogue of 5-HT (i.e., 4) and of 5-methoxytryptamine (i.e., 5) were prepared and compared with 8-OH-DPAT with respect to their binding profile. Unlike 8-OH-DPAT, neither compound 4 nor 5 displays selectivity for 5-HT1A vs 5-HT2 sites. Consistent with these results, stimulus generalization occurs with 5 both in rats trained to discriminate 8-OH-DPAT from saline and in rats trained to discriminate the 5-HT2 agonist DOM from saline. The results of this study suggest that it is not the N,N-dipropyl groups that account for selectivity, but, rather, it is some feature associated with the pyrrole portion of the indolylalkanamines that is important.
Glennon
R A
RA
Department of Medicinal Chemistry/School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0581.
Titeler
M
M
Lyon
R A
RA
Slusher
R M
RM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001665:Binding Sites; D004193:Discrimination Learning / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; C055436:N,N-di-n-propylserotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin