Skip to main content

Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain.

Publication ,  Journal Article
Reches, A; Burke, RE; Kuhn, CM; Hassan, MN; Jackson, VR; Fahn, S
Published in: J Pharmacol Exp Ther
June 1983

Tetrabenazine (TBZ) is used in the treatment of hyperkinetic movement disorders. Its effect is thought to be mediated by depletion of dopamine (DA) stores. We studied other possible mechanisms of action of this drug. TBZ decreased DA concentration in rat striatum and nucleus accumbens in a dose-dependent manner with an IC50 of approximately 1.2 mg.kg-1. Maximal depletion was obtained within 30 min with only partial recovery at 8 hr. TBZ induced (at 40 mg . kg-1) 5- to 8-fold increases in 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations in both brain regions. Unlike reserpine, TBZ completely abolished the apomorphine-induced inhibition of DA synthesis under conditions in which this effect is mediated by presynaptic DA receptors. Both TBZ (5 mg . kg-1) and reserpine (5 mg . kg-1) depleted, at 1 hr, striatal DA content by approximately 90%. However, TBZ, but not reserpine, significantly stimulated in vivo tyrosine hydroxylase activity. TBZ also inhibited [3H]spiperone binding in the striatum with Ki = 2.1 X 10(-6) M. In rats, with unilateral destruction of the nigrostriatal pathway with 6-hydroxydopamine, pretreatment with TBZ significantly reduced the number of rotations induced by apomorphine. Finally, in rats treated with either TBZ (5 mg . kg-1) or reserpine (5 mg . kg-1), prolactin levels significantly increased as compared to control values. TBZ, but not reserpine, blocked apomorphine inhibition of prolactin secretion. We conclude that, in addition to depleting monoamines, TBZ also blocks both presynaptic and postsynaptic DA receptors in rat brain.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1983

Volume

225

Issue

3

Start / End Page

515 / 521

Location

United States

Related Subject Headings

  • Tetrabenazine
  • Reserpine
  • Receptors, Dopamine
  • Rats, Inbred Strains
  • Rats
  • Prolactin
  • Pharmacology & Pharmacy
  • Nucleus Accumbens
  • Male
  • Dopamine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reches, A., Burke, R. E., Kuhn, C. M., Hassan, M. N., Jackson, V. R., & Fahn, S. (1983). Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain. J Pharmacol Exp Ther, 225(3), 515–521.
Reches, A., R. E. Burke, C. M. Kuhn, M. N. Hassan, V. R. Jackson, and S. Fahn. “Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain.J Pharmacol Exp Ther 225, no. 3 (June 1983): 515–21.
Reches A, Burke RE, Kuhn CM, Hassan MN, Jackson VR, Fahn S. Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain. J Pharmacol Exp Ther. 1983 Jun;225(3):515–21.
Reches, A., et al. “Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain.J Pharmacol Exp Ther, vol. 225, no. 3, June 1983, pp. 515–21.
Reches A, Burke RE, Kuhn CM, Hassan MN, Jackson VR, Fahn S. Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain. J Pharmacol Exp Ther. 1983 Jun;225(3):515–521.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1983

Volume

225

Issue

3

Start / End Page

515 / 521

Location

United States

Related Subject Headings

  • Tetrabenazine
  • Reserpine
  • Receptors, Dopamine
  • Rats, Inbred Strains
  • Rats
  • Prolactin
  • Pharmacology & Pharmacy
  • Nucleus Accumbens
  • Male
  • Dopamine