Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus. 1989

D D Truong, and M P Galloway, and G Pezzoli, and Z Jamrozik, and S Fahn
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009207 Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). Myoclonus, Action,Myoclonus, Nocturnal,Myoclonus, Palatal,Polymyoclonus,Myoclonic Jerk,Myoclonic Jerking,Myoclonus Simplex,Myoclonus, Eyelid,Myoclonus, Intention,Myoclonus, Lower Extremity,Myoclonus, Oculopalatal,Myoclonus, Segmental,Myoclonus, Sleep,Myoclonus, Upper Extremity,Action Myoclonus,Extremity Myoclonus, Lower,Extremity Myoclonus, Upper,Eyelid Myoclonus,Intention Myoclonus,Jerk, Myoclonic,Jerking, Myoclonic,Jerks, Myoclonic,Lower Extremity Myoclonus,Myoclonic Jerks,Nocturnal Myoclonus,Oculopalatal Myoclonus,Palatal Myoclonus,Segmental Myoclonus,Simplex, Myoclonus,Sleep Myoclonus,Upper Extremity Myoclonus
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D003634 DDT A polychlorinated pesticide that is resistant to destruction by light and oxidation. Its unusual stability has resulted in difficulties in residue removal from water, soil, and foodstuffs. This substance may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP-85-002, 1985). (From Merck Index, 11th ed) 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane,4,4'-DDT,4,4'-Dichlorodiphenyltrichloroethane,Benzochloryl,Chlorophenothane,TbisC-ethane,p',p'-DDT,4,4' DDT,4,4' Dichlorodiphenyltrichloroethane,TbisC ethane
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000081 Acetamides Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine

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