| Abstract | The separate and combined effects of successive administration of amantadine, 100 mg/kg, i.p., and chlorpromazine, 0.2 mg/kg, i.p., on motor activity and whole brain levels of certain biogenic amines and major metabolites were studied in four strains of mice. These were the albino ICR, the inbred BALB/C, C57BL/6 and the hybrid CDF-I mice. Amantadine produced a strain-dependent behavioral stimulation subsequent the fourth dose. This was apparent in ICR and C57BL/6 mouse strains and was followed by a behavioral depression phase occurring during the night in C57BL/6 mice which was antagonized by chlorpromazine. Administration of chlorpromazine alone affected only CDF-1 mouse mobility. Chlorpromazine reduced only ICR mouse brain dopamine without concomitant changes in major acid metabolites. Repeated administration of amantadine prior to chlorpromazine negated this effect. Chlorpromazine enhancement of BALB/C brain serotonin and 5-hydroxyindoleacetic acid was antagonised by pretreatment with amantadine. This antagonism was also evident in BALB/C mouse brain dihydroxyphenylacetic acid. The results suggest genotypic-dependent behavioral and cerebral effects by the drugs studied. The antagonism between amantadine and chlorpromazine on brain amines may explain the therapeutic efficacy of amantadine in modulating chlorpromazine-induced extrapyramidal disorders. |
| Authors | F S Messiha
(Affiliation: Department of Pharmacology, University of North Dakota School of Medicine, Grand Forks 58203.)
|
| Journal | Neurotoxicology
(Neurotoxicology)
Vol. 12
Issue 3
Pg. 571-81
( 1991)
ISSN: 0161-813X UNITED STATES |
| PMID | 1745440
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Chlorpromazine
- Amantadine
|
| Topics |
- Amantadine
(therapeutic use)
- Animals
- Basal Ganglia Diseases
(chemically induced, drug therapy, genetics)
- Chlorpromazine
(antagonists & inhibitors, toxicity)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Inbred ICR
- Motor Activity
(drug effects)
- Rats
- Rats, Inbred Strains
- Species Specificity
|
