Chronic treatment with the D1 receptor antagonist, SCH 23390, and the D2 receptor antagonist, raclopride, in cebus monkeys withdrawn from previous haloperidol treatment. Extrapyramidal syndromes and dopaminergic supersensitivity. 1993

H Lublin, and J Gerlach, and L Peacock
St Hans Hospital, Department P, Roskilde, Denmark.

The effects of chronic treatment with dopamine (DA) D1 and D2 receptor antagonists were evaluated in eight cebus apella monkeys with mild oral dyskinesia after previous haloperidol treatment. SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists. Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously. SCH 23390 and raclopride induced dystonic syndromes, catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of SCH 23390, while they showed increased sensibility to the dystonic effect of raclopride. Baseline oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment. SCH 23390 induced supersensitivity to the oral dyskinesia- and grooming-inducing effects of SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of SCH 23390 and the unchanged baseline oral dyskinesia during SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade.

UI MeSH Term Description Entries
D006993 Hypnotics and Sedatives Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Hypnotic,Sedative,Sedative and Hypnotic,Sedatives,Hypnotic Effect,Hypnotic Effects,Hypnotics,Sedative Effect,Sedative Effects,Sedatives and Hypnotics,Effect, Hypnotic,Effect, Sedative,Effects, Hypnotic,Effects, Sedative,Hypnotic and Sedative
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D002428 Cebus A genus of the family CEBIDAE, subfamily CEBINAE, consisting of gracile or untufted capuchin species. Tufted capuchins belong to genus SAPAJUS. Members include C. capucinus, C. nigrivultatus, and C. albifrons. Cebus inhabits the forests of Central and South Americas. Cebu,Gracile Capuchins,Monkey, Capuchin,Monkey, Ring-Tail,Monkey, Ringtail,Monkey, Ringtailed,Untufted Capuchins,White-Fronted Capuchin,Monkey, Ring-Tailed,Capuchin Monkey,Capuchin Monkeys,Capuchin, Gracile,Capuchin, Untufted,Capuchin, White-Fronted,Gracile Capuchin,Monkey, Ring Tail,Monkey, Ring Tailed,Ring-Tail Monkey,Ring-Tail Monkeys,Ring-Tailed Monkey,Ring-Tailed Monkeys,Ringtail Monkey,Ringtail Monkeys,Ringtailed Monkey,Ringtailed Monkeys,Untufted Capuchin,White Fronted Capuchin,White-Fronted Capuchins
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006120 Grooming An animal's cleaning and caring for the body surface. This includes preening, the cleaning and oiling of feathers with the bill or of hair with the tongue. Preening,Groomings,Preenings
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol
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

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