Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.
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PMID:Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat. 613 32

Buspirone, a 5-HT (5-hydroxytryptamine, serotonin)(1A) partial agonist, is being used as an anxiolytic drug. The mechanism of action is explained by an effect on the 5-HT system. The main source of 5-HT in the forebrain is the dorsal raphe nucleus (DRN). However, there are also other populations of non-5-HT neurons in the DRN. Here, we investigated the effect of acute and chronic buspirone treatments on the 5-HT and non-5-HT cells, the neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase (TH) cells, in the DRN. Rats received either an acute or chronic administration of buspirone or saline. Hereafter, the brains were processed for 5-HT, nNOS, and TH immunohistochemistry. We found that acute and chronic buspirone treatments significantly lowered the mean optical density of nNOS in the DRN as compared to controls. Meanwhile only the chronic buspirone treatment reduced the mean density of 5-HT and TH immunoreactivity but not the acute buspirone as compared to saline treated animals. Our findings suggest that buspirone treatment affects not only the intracellular content of 5-HT but also nNOS and TH. Therefore, the cellular effect of buspirone is more complex than thought.
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PMID:Buspirone-induced changes in the serotonergic and non-serotonergic cells in the dorsal raphe nucleus of rats. 2017 29