The most desirable conformation of phenylethylamine (PEA) moiety stimulating noradrenergic neurons: effects of PEA, methamphetamine, phenelzine, methylphenidate, nomifensine and mazindol on rat spinal reflexes.
1. The effects of phenylethylamine (PEA) and PEA-related substances on the rat spinal monosynaptic reflex (MSR) were examined. According to the flexibility of the PEA moiety in the molecule, these drugs were classified into three groups, i.e. non-rigid, rigid and semi-rigid groups. 2. PEA, methamphetamine and phenelzine (non-rigid group) showed opposite effects on the MSR, an increase at low doses and a decrease at high doses. The former effect was antagonized by pretreatment with the alpha 1-blocker, prazosin. 3. Nomifensine and mazindol (rigid group), which share the similar spatial relationships between the aromatic moiety and nitrogen, increased the MSR, and this effect was blocked by prazosin. 4. In the semi-rigid group the same result was obtained for methylphenidate but not for 1-methyl-2-benzylpiperidine, which might have difficulty in having the similar conformation of PEA moiety as methylphenidate because of its methyl group. 5. From these results, it appears that the effects of PEA and amphetamines on the MSR are determined by the spatial relationships between the amino group and the aromatic moiety and that the enhancement of the MSR might be induced through alpha 1-adrenergic transmission.
Hasebe
Y
Y
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Ono
H
H
Fukuda
H
H
Ohta
S
S
Hirobe
M
M
D000818:Animals; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D008968:Molecular Conformation; D009474:Neurons / Q000187:drug effects*; D009627:Nomifensine / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010624:Phenelzine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*
D010627:Phenethylamines; D009627:Nomifensine; D008774:Methylphenidate; D008694:Methamphetamine; D008454:Mazindol; D006220:Haloperidol; D010624:Phenelzine; D009638:Norepinephrine