Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats.
The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N-methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2-aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens.
Ono
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Hasebe
Y
Y
Mori
T
T
Fukuda
H
H
Kohno
M
M
Ohta
S
S
Hirobe
M
M
D000818:Animals; D008297:Male; D008968:Molecular Conformation; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013131:Spine / Q000502:physiology*; D013329:Structure-Activity Relationship
D010627:Phenethylamines; D012702:Serotonin Antagonists