In Vitro Inhibition of Noradrenaline‐<sup>3</sup>H Uptake by Reserpine and Tetrabenazine in Mouse Cerebral Cortex Tissues

Ross, Svante B.; Renyi, A. L.

doi:10.1111/j.1600-0773.1966.tb00370.x

Cited by 8 publications

(1 citation statement)

References 15 publications

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“…Thus, TBZ is 2.5-fold selective for VMAT2 over DAT and 56-fold selective for VMAT2 over SERT. Of further note, previous research has shown that TBZ inhibits the norepinephrine transporter (NET) across a concentration range similar to that inhibiting DAT and SERT (IC 50 = 0.5 μM; Ross and Renyi, 1966). In comparison, lobelane is 35-fold selective for VMAT2 over DAT and 80-fold selective for VMAT2 over SERT.…”

Section: Discussionmentioning

confidence: 96%

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

et al. 2011

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Tetrabenazine (TBZ), a benzoquinolizine derivative, binds with high affinity to the vesicular monoamine transporter-2 (VMAT2), inhibiting uptake of cytosolic monoamines. The current study aimed to provide preclinical evidence supporting the potential use of TBZ as a treatment for methamphetamine abuse. Effects of TBZ on function of the dopamine transporter (DAT) and serotonin transporter (SERT) in striatal and hippocampal synaptosomes, respectively, and on VMAT2 function in isolated striatal synaptic vesicles were determined. Effect of TBZ (acute, 0.1 - 3.0 mg/kg, s.c.; repeated, 1.0 mg/kg for 7 days) on locomotor activity in methamphetamine-sensitized rats was assessed. Ability of TBZ (0.1 -3.0 mg/kg; s.c.) or vehicle to decrease the discriminative effect of methamphetamine also was determined. Ability of TBZ (acute, 0.1 - 1.0 mg/kg, s.c.; repeated, 0.1 or 1.0 mg/kg for 7 days) to specifically decrease methamphetamine self-administration was determined; for comparison, a separate group of rats was assessed for effects of TBZ on food-maintained responding. Results show that TBZ was 11-fold more potent inhibiting DAT than SERT, and 2.5-fold more potent inhibiting VMAT2 than DAT. Results from behavioral studies showed that the lowest dose of TBZ transiently increased methamphetamine self-administration, whereas higher TBZ doses decreased methamphetamine self-administration. Also, TBZ at high doses decreased methamphetamine locomotor sensitization and discriminative stimulus effects, as well as food-maintained responding. Thus, despite acting as a potent VMAT2 inhibitor, these preclinical results indicate that TBZ lacks behavioral specificity as an inhibitor of methamphetamine-induced reinforcement, diminishing its viability as a suitable treatment for methamphetamine abuse.

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Section: Discussionmentioning

confidence: 96%

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

et al. 2011

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Tetrabenazine has properties of a dopamine receptor antagonist

Cronin

MacLeod

1982

Annals of Neurology

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Tetrabenazine is considered to act in a manner similar to reserpine to reduce the involuntary movements of tardive dyskinesia or Huntington's disease and to improve psychoses. We determined that tetrabenazine also has properties of a dopamine receptor antagonist by testing the ability of tetrabenazine to block the inhibitory effect of dopamine on prolactin secretion from rat anterior pituitary glands in vitro and to displace 3H-spiperone binding to dopamine receptors in the pituitary, corpus striatum, and a rat transplantable prolactin-secreting tumor. Under in vitro conditions, 0.5 to 10 microM tetrabenazine directly blocked dopaminergic inhibition of prolactin secretion. Furthermore, 1 hour after tetrabenazine injection (30 mg/kg intraperitoneally) in vivo, when the serum prolactin had increased from 22 +/- 9 to 450 +/- 52 ng/ml (p less than 0.01), pituitary glands of the treated rats examined in vitro were refractory to dopaminergic inhibition of prolactin release. Tetrabenazine apparently interacts with the dopamine receptor because this drug displaced the dopamine antagonist 3H-spiperone from dopamine receptors of the three different tissues with an apparent inhibitory constant of about 5 microM. We conclude that tetrabenazine has biological and pharmacological properties typical of a dopamine receptor antagonist. These observations should stimulate a reevaluation of the mechanisms for the actions of tetrabenazine previously attributed exclusively to a "reserpine-like" effect.

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Transport of Monosaccharides, Amines, and Certain Other Metabolites

Neame

1970

Control Mechanisms in the Nervous System

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In Vitro Inhibition of Noradrenaline‐³H Uptake by Reserpine and Tetrabenazine in Mouse Cerebral Cortex Tissues

Cited by 8 publications

References 15 publications

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

Tetrabenazine has properties of a dopamine receptor antagonist

Transport of Monosaccharides, Amines, and Certain Other Metabolites

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In Vitro Inhibition of Noradrenaline‐3H Uptake by Reserpine and Tetrabenazine in Mouse Cerebral Cortex Tissues

Cited by 8 publications

References 15 publications

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

Tetrabenazine has properties of a dopamine receptor antagonist

Transport of Monosaccharides, Amines, and Certain Other Metabolites

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Product

Resources

About

In Vitro Inhibition of Noradrenaline‐³H Uptake by Reserpine and Tetrabenazine in Mouse Cerebral Cortex Tissues