5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices.

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Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Chaki S, Aihara H

5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices.

Eur J Pharmacol. 1988 Aug 9;153(1):89-95.

PubMed ID

2975224 [ View in PubMed

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Abstract

5-Hydroxytryptamine (5-HT) inhibited the K+-induced [3H]dopamine [( 3H]DA) release from slices of rat striatum. Minaprine (3-(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine) attenuated the inhibitory effect of 5-HT in a dose-dependent manner. 5-HT2 receptor antagonists, ketanserin and mianserin, prevented the effect of 5-HT as well as minaprine did. The inhibitory effect of 5-HT was not mimicked by a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and was not prevented by a 5-HT1A and 5-HT1B mixed receptor antagonist, propranolol. Minaprine was a potent inhibitor of the binding of [3H]ketanserin to binding sites in the striatum over the concentration range 10(-6)-10(-4) M. Lesion of the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) significantly reduced the K+-induced [3H]DA release from the striatum and release was no longer inhibited by 5-HT. Lesioning, however, did not change significantly the [3H]ketanserin binding in the striatum. These results suggest that minaprine suppresses the inhibitory effect of 5-HT on DA release in the striatum via the inhibition of 5-HT binding at the 5-HT2 receptor on the nerve terminal of the DA-ergic neuron and, further, that the proportion of the 5-HT2 receptor site which is located on the nerve terminal of the DA-ergic neuron is small in the striatum.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Minaprine	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details
Minaprine	5-hydroxytryptamine receptor 2B	Protein	Humans	Yes	Antagonist	Details
Minaprine	5-hydroxytryptamine receptor 2C	Protein	Humans	Yes	Antagonist	Details