Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus.
Milacemide, a glycine prodrug that is able to enter the brain readily, has been shown to have an antimyoclonic property in the p,p'-DDT-induced myoclonus syndrome. Milacemide increased regional 5-HT and dopamine and decreased 5-HIAA, DOPAC and HVA levels in naive rats. In p,p'-DDT-treated rats, 5-HT levels were unchanged at the time the rats experienced spontaneous myoclonus in all brain regions except in the striatum, where it increased. 5-HIAA levels increased but did not reach significant levels except in the striatum. Dopamine, DOPAC, HVA and norepinephrine were unchanged. When rats were treated concurrently with both p,p'-DDT and milacemide, regional 5-HT levels were increased and NE levels in the brainstem and cerebellum decreased. Depletion of brain serotonin by pretreatment with PCPA or with 5,7-DHT, or blocking 5-HT receptors with different 5-HT antagonists, failed to eliminate the antimyoclonic property of milacemide. This antimyoclonic effect of milacemide may be mediated through other mechanisms besides its ability to increase brain 5-HT levels. Possible mechanisms to be considered are its antiepileptic property, and its ability to increase brain glycine levels. Milacemide may have potential for therapeutic trials in patients with myoclonus.
Truong
D D
DD
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY.
Galloway
M P
MP
Pezzoli
G
G
Jamrozik
Z
Z
Fahn
S
S
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000032:analysis; D001923:Brain Chemistry / Q000187:drug effects*; D003634:DDT / Q000009:adverse effects; D004298:Dopamine / Q000032:analysis*; D008297:Male; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis*
D000081:Acetamides; D000927:Anticonvulsants; D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; C039332:milacemide; D012701:Serotonin; D003634:DDT; D004298:Dopamine