Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats.
Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The 'methylphenidate group' also increased brain 3,4-dihydroxyphenylacetic acid (DOPAC) in naive rats; whereas the '(+)-amphetamine group' decreased DOPAC in naive rats, as well as in reserpinized rats, alpha-methyl-p-tyrosine-treated rats and after acute hemisection. The reserpine antagonism of the 'methylphenidate group'-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The '(+)-amphetamine group'-induced stereotyped behaviour was not blocked by short time pretreatment with alpha-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the '(+)-amphetamine group'.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects
D000662:Amphetamines; D000928:Antidepressive Agents; D007546:Isoquinolines; D008781:Methyltyrosines; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D008774:Methylphenidate; D012110:Reserpine; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid