Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.
The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species.
Parkinson's Disease Society Experimental Research Laboratories, Biomedical Sciences Division, King's College, London, U.K.
K W
KW
Lange
P A
PA
Löschmann
H
H
Wachtel
R
R
Horowski
P
P
Jähnig
P
P
Jenner
C D
CD
Marsden
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002144:Callithrix; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D008090:Lisuride / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D000978:Antiparkinson Agents; D015259:Dopamine Agents; C006208:dironyl; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008090:Lisuride