Tetrabenazines

Terolidine 2, 56 Tesicam T79 Tesimide 296 Testolactone 160 Testosterone cypionate 1, 172 Testosterone decanoate T, 172 Testosterone propionate 1, 172 Tetrabenazine 350 Tetracaine 1, 110 Tetracycline 1, 212 Tetrahydrocannabinol, A-1, 1, 394... 

Carbet hoxy methyl-6,7-dimethoxy-1, 3,4-tetrahydroisoquinoline Tetrabenazine... 

VMATs are irreversibly inhibited by the potent antihypertensive drug reserpine. The depressive effects of reserpine helped to formulate the original monoamine hypothesis of affective disorders. Reseipine also appears to interact with the transporters near the site of substrate recognition. Tetrabenazine, which is used in treatment of movement disorders, inhibits VMAT2 much more potently than VMAT1, consistent with the less hypotensive action of this agent. 

Most DA (up to 75%) is stored in vesicles like NA. This can be disrupted by the rauwolfia alkaloid, reserpine and by drugs like tetrabenazine. It should be emphasised that these drugs deplete the neurons of amines by stopping their incorporation into... 

Blockers Nisoxetine, desipramine GBR12909, RTI-121 Reserpine, tetrabenazine... 

Both enantiomers and the racemate of l-(3,4-dichlorophenyl)-3-azabicyclo [3.1.0]hexane, 27a-c, have been reported to be in development. The racemate, DOV 216,303, inhibits the reuptake of NE, 5-HT and DA with IC50 values of 20, 14 and 78 nM, respectively [85]. DOV 216,303 is active in tests predictive of antidepressant activity, including the mouse FST (minimum effective dose = lOmg/kg), reversal of tetrabenazine-induced ptosis and locomotor depression. DOV 216,303 was also reported to be well tolerated in phase I clinical trials [85,86], In a phase II study designed to explore safety and tolerability in depressed individuals, patients received either DOV 216,303 (50 mg, b.i.d.) or citalopram (20 mg, b.i.d.) for two weeks [85]. It was found that the side effect profile was not remarkably different between the two treatment groups. In addition, time-dependent reductions in Hamilton Depression Scores (HAM-D) were similar for both groups. 

In Huntington s chorea, tetrabenazine is used to control movement disorders. It probably causes a depletion of nerve endings of dopamine. However, it has a useful action in only a proportion of patients and its use may be limited by the development of depression, a symptom that may already be present due to the underlying disease itself. 

Tetrabenazine, 350 Tetracaine, 10 Tetracycline, 212, 213 A -Tetrahydrocannabinol, 394 Tetrahydropyrimidines, synthesis, 266... 

Tetrabenazine is a non-neuroleptic that is a weak post-synaptic antagonist of dopamine and depletes presyn-... 

Jankovic, J. and Orman, J. (1988) Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology 38 391-394. 

In summary, treatments for tardive dyskinesia include cessation of the neuroleptic switching to a novel agent cholinergic agents and dopamine depleting drugs, such as reserpine or tetrabenazine. 

Reserpine depletes cerebral dopamine by preventing intraneuronal storage (see Chapter 6) it is introduced in low doses (eg, 0.25 mg daily), and the daily dose is then built up gradually (eg, by 0.25 mg every week) until benefit occurs or adverse effects become troublesome. A daily dose of 2-5 mg is often effective in suppressing abnormal movements, but adverse effects may include hypotension, depression, sedation, diarrhea, and nasal congestion. Tetrabenazine (12.5-50 mg orally three times daily) resembles reserpine in depleting cerebral dopamine and has less troublesome adverse effects it is now available in the USA. Treatment with postsynaptic dopamine receptor blockers such as phenothiazines and... 

Tetrabenazine, reserpine Deplete amine transmitters, especially dopamine, from nerve endings Reduce chorea severity Huntington s disease other applications, see Chapter 11 Oral Toxicity Hypotension, sedation, depression, diarrhea tetrabenazine somewhat less toxic... 

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