Effects of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain in vivo

The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, p...

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Bibliographic Details
Published in:Metabolic brain disease 1991-09, Vol.6 (3), p.111-124
Main Authors: Kondoh, Y, Mizusawa, S, Murakami, M, Nagata, K, Nakamichi, H, Watanabe, K
Format: Article
Language:English
Subjects:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives
Animals
Brain - drug effects
Brain - metabolism
Calcium - antagonists & inhibitors
Dopamine - analysis
Dopamine - metabolism
Isoquinolines - pharmacology
Male
Rats
Rats, Inbred Strains
Serotonin - analysis
Serotonin - metabolism
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Summary:The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, parallel increases of both serotonin (5-HT) and 5-HIAA levels were observed at 0.3 mg/kg, but only the 5-HT level increased at 0.1 mg/kg. These results suggest that HA1077 may activate the turnover or synthesis of 5-HT. After administration of HA1077 at 0.3, 1, and 3 mg/kg, the dopamine (DA) level was increased in the striatum, but 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels were unchanged. After HA1077 administration at 1 mg/kg, both DA and DOPAC levels increased in the hypothalamus and only DA level increased in the cerebral cortex. By contrast, DOPAC level decreased in the midbrain after HA1077 treatment at 0.1 and 0.3 mg/kg, and in the brainstem at 0.1 and 10 mg/kg. The ratio of [3H]-N-methylspiperone accumulation relative to that in the cerebellum did not change after HA1077 treatment at any of the doses employed. Thus, the effects of HA1077 on neurotransmitter metabolism are complex and vary depending on the dosage and sites of the brain. Although the dose-dependent effects of HA1077 on neurotransmitter metabolism are similar to those of calcium entry blockers, HA1077 can facilitate DA synthesis in the hypothalamus and striatum, unlike the calcium entry blockers.
ISSN:0885-7490
DOI:10.1007/BF00996903