Biomedical subjects

J K Ritter

Publications and source records attributed to J K Ritter.

39 records · Page 3Linked to original sources

PubMed1985

Role of dopamine in the neurotoxic effects of methamphetamine.

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, antagonizes this effect of methamphetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, alpha-methyl-p-tyrosine no longer prevented the effects of methamphetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the serotonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptophan hydroxylase was also dependent on catecholamine synthesis. These results suggest that dopamine plays an important role in the changes mediated by the administration of methamphetamine in both the dopaminergic and serotonergic systems.

Animals↗

PubMed1984

Increases of substance P-like immunoreactivity within striatal-nigral structures after subacute methamphetamine treatment.

Substantial increases in the nigral concentration of substance P-like immunoreactivity (SPLI) were observed after subacute administration of the indirect dopamine agonist, methamphetamine (METH, 15 mg/kg every 6 hr; five doses). The effect was opposite, and thus consistent, with the reduction of SPLI levels previously reported in nigral tissue after pharmacological blockade of the nigrostriatal dopaminergic activity. In addition, subacute METH treatment increased SPLI concentrations in other structures associated with the basal ganglia, such as the striatum and entopeduncular nucleus, but not in the hypothalamus or dorsal raphe nucleus. Subacute treatment with d-amphetamine exerted METH-like effects on the substance P neurons of the basal ganglia, whereas haloperidol completely antagonized the METH effect. The possibility that monoaminergic systems help mediate the response of the substance P system to subacute METH treatment is examined.

Animals↗

PubMedDate not supplied

Induction and inhibition of rat hepatic drug metabolism by N-substituted imidazole drugs.

Three daily administrations of N-substituted imidazole antimycotics, clotrimazole (CloTZ, 75 mg/kg/day), miconazole (MCZ, 150 mg/kg/day), or tioconazole (TCZ, 150 mg/kg/day), but not the 4,5-disubstituted imidazole cimetidine (350 mg/kg/day) or imidazole (200 mg/kg/day for 4 days), induced rat hepatic cytochrome P-450 and other drug-metabolizing enzymes. These findings paralleled in vitro observations where CloTZ, MCZ, and TCZ were several orders of magnitude more potent as inhibitors of p-nitroanisole O-demethylase activity in control male rat liver microsomes than cimetidine or imidazole. Although no marked difference in inhibitory potency was evident among the N-substituted imidazoles, there were qualitative and quantitative differences in the profiles and extents of induction of various cytochrome P-450-dependent monooxygenases and Phase II conjugation enzymes. Cytochrome P-450 was elevated dramatically by CloTZ (3-4 times the control) and to a lesser extent by MCZ and TCZ (congruent to 1.5 times the control). For all agents, there was an increase in metyrapone binding approximately equivalent to the additional (i.e. above control) cytochrome P-450. Despite the large difference in cytochrome P-450 induction by CloTZ, MCZ, and TCZ, these agents elevated p-nitroanisole demethylase and aniline hydroxylase to similar extents (3-5 X and 1-2 X control, respectively). All agents induced erythromycin and ethylmorphine demethylation in proportion to cytochrome P-450. Ethoxyresorufin O-de-ethylation was not substantially affected by any agent. Large differences in the extent and specificity of induction of microsomal glucuronide conjugations were also evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗