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Chemical Compound Review

Trivastal     2-[4-(benzo[1,3]dioxol-5...

Synonyms: Trivastan, piribedil, Piribedile, Piribendyl, Piribedilum, ...
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Disease relevance of Trivastal

  • Three patients with Parkinson's disease had so-called sleep attacks at the wheel while taking bromocryptine, lisuride pergolide, or piribedil [1].
  • Piribedil: its synergistic effect in multidrug regimens for parkinsonism [2].
  • In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality [3].
  • In contrast, a 10 times higher infusion rate, 5 micrograms/kg/min, did not antagonize the following DA2-mediated responses: increase in femoral blood flow produced by apomorphine and piribedil in untreated dogs; and N,N-di-n-propyl DA (DPDA)-induced inhibition of the tachycardia produced by cardiac accelerator nerve stimulation [4].
  • Piribedil decreased tremor but facilitated EMG activity in tardive dyskinesia [5].

Psychiatry related information on Trivastal

  • Mice that had received the chronic morphine treatment were found to require significantly less apomorphine to produce an increase in locomotor activity, and they exhibited a significantly greater hypothermic response to piribedil than did morphine-naive mice [6].
  • RESULTS: Piribedil showed a beneficial effect on the acquisition of a problem-solving routine, depending on the age of subjects, as revealed by solution reliability indexes measures [7].
  • Thirteen consecutive patients with restless legs syndrome (RLS) were treated with piribedil and were rated using an RLS rating scale (0-10) and subjective response (0-100%); 11/13 (85%) had improvement of their mean RLS scores with subjective response ranging from 30% to 100% (mean 74.6%) [8].
  • It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems [9].
  • A new carbon paste electrode selective for piribedil (PD) was prepared and fully characterized in terms of composition, usable pH range, response time and thermal stability [10].

High impact information on Trivastal

  • In baboons, the intravenous administration of piribedil, a dopaminergic agonist, was associated with marked dose dependent increases in CBF and cerebral oxygen consumption [11].
  • We have studied the effects of piribedil on CBF in 20 normal, human volunteers of comparable ages [11].
  • The synergistic effect of Piribedil and other antiparkinsonian drugs emphasizes the need for careful titration of all available medications in difficult cases and demonstrates the usefulness of dopamine receptor stimulators when drugs acting presynaptically have failed [2].
  • However, piribedil had no effect on release of [3H]DA from the median eminence of rats with tumors [12].
  • Finally, in analogy to the frontal cortex, piribedil likewise elicited a dose-dependent increase in extracellular levels of ACh in the dorsal hippocampus [13].

Chemical compound and disease context of Trivastal


Biological context of Trivastal


Anatomical context of Trivastal


Associations of Trivastal with other chemical compounds


Gene context of Trivastal

  • The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of Parkinson's disease [32].
  • There was no difference in the half-life of SAM-DC activity between piribedil-treated rats and controls [27].
  • In the first experiment, REM deprived rats displayed much aggressiveness when challenged with 10 and 20 mg/kg of bromocriptine and piribedil [33].
  • Piribedil inhibition of prolactin release induced by mechanical breast emptying in puerperal women [34].
  • Both apomorphine and piribedil reduced serum PRL and TSH levels, stimulated GH release at low but not at high doses and either had no effect or tended to reduce serum LH levels [35].

Analytical, diagnostic and therapeutic context of Trivastal

  • METHOD: In a 90-day randomized double-blind study, treatment with piribedil was compared to placebo in 60 patients with clinically diagnosed mild cognitive impairment and a Mini-Mental State Examination (MMSE) score of 21 to 25 [36].
  • Rats experienced in amphetamine self-administration readily initiated and maintained responding for apomorphine and piribedil [37].
  • Subjects were evaluated at baseline, and after 2 months of a placebo or piribedil (50 mg daily) treatment in a double-blind, crossover design [7].
  • Oral administration of ET-495 was found to cause worsening of psychiatric status in 4 out of 7 schizophrenic patients, and to induce a paranoid state and a syndrome of auditory hallucinosis in 2 non-schizophrenics [38].
  • Subcutaneous injections of low doses of apomorphine (0.05-0.25 mg/kg) or piribedil (0.2-1.0 mg/kg), which preferentially activate presynaptic dopamine autoreceptors at those doses, evoked yawning [30].


  1. Sleep attacks and Parkinson's disease treatment. Ferreira, J.J., Galitzky, M., Montastruc, J.L., Rascol, O. Lancet (2000) [Pubmed]
  2. Piribedil: its synergistic effect in multidrug regimens for parkinsonism. Feigenson, J.S., Sweet, R.D., McDowell, F.H. Neurology (1976) [Pubmed]
  3. Reversibility of hemodynamic hypofrontality in schizophrenia. Geraud, G., Arné-Bès, M.C., Güell, A., Bes, A. J. Cereb. Blood Flow Metab. (1987) [Pubmed]
  4. Separation of peripheral dopamine receptors by a selective DA1 antagonist, SCH 23390. Goldberg, L.I., Glock, D., Kohli, J.D., Barnett, A. Hypertension (1984) [Pubmed]
  5. EMG patterns in abnormal involuntary movements induced by neuroleptics. Bathien, N., Koutlidis, R.M., Rondot, P. J. Neurol. Neurosurg. Psychiatr. (1984) [Pubmed]
  6. Blockage of narcotic-induced dopamine receptor supersensitivity by cyclo(Leu-Gly). Ritzmann, R.F., Walter, R., Bhargava, H.N., Flexner, L.B. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  7. Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil. Peretti, C.S., Gierski, F., Harrois, S. Psychopharmacology (Berl.) (2004) [Pubmed]
  8. Piribedil for restless legs syndrome: a pilot study. Evidente, V.G. Mov. Disord. (2001) [Pubmed]
  9. Apomorphine and piribedil in rats: biochemical and pharmacologic studies. Butterworth, R.F., Poignant, J.C., Barbeau, A. Advances in neurology. (1975) [Pubmed]
  10. Chemically modified carbon paste electrode for the potentiometric flow injection analysis of piribedil in pharmaceutical preparation and urine. Ibrahim, H. Journal of pharmaceutical and biomedical analysis. (2005) [Pubmed]
  11. Effects of a dopaminergic agonist (piribedil) on cerebral blood flow in man. Güell, A., Géraud, G., Jauzac, P., Victor, G., Arné-Bès, M.C. J. Cereb. Blood Flow Metab. (1982) [Pubmed]
  12. Decline of tuberoinfundibular dopaminergic function resulting from chronic hyperprolactinemia in rats. Sarkar, D.K., Gottschall, P.E., Meites, J. Endocrinology (1984) [Pubmed]
  13. Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors. Gobert, A., Di Cara, B., Cistarelli, L., Millan, M.J. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  14. The Dopamine Agonist Piribedil with L-DOPA Improves Attentional Dysfunction: Relevance for Parkinson's Disease. Turle-Lorenzo, N., Maurin, B., Puma, C., Chezaubernard, C., Morain, P., Baunez, C., Nieoullon, A., Amalric, M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  15. Parkinsonism by haloperidol and piribedil. Corsini, G.U., Del Zompo, M., Spissu, A., Mangoni, A., Gessa, G.L. Psychopharmacology (Berl.) (1978) [Pubmed]
  16. Effects of apomorphine and piribedil on pentylenetetrazol-induced seizures in mice. Riffee, W.H., Wilcox, R.E., Goldman, C.P., Smith, R.V. Psychopharmacology (Berl.) (1981) [Pubmed]
  17. Identification of amino Acid determinants of dopamine 2 receptor synthetic agonist function. Al-Fulaij, M.A., Ren, Y., Beinborn, M., Kopin, A.S. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  18. The Parkinson-Control study: A 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease. Castro-Caldas, A., Delwaide, P., Jost, W., Merello, M., Williams, A., Lamberti, P., Aguilar, M., Del Signore, S., Cesaro, P. Mov. Disord. (2006) [Pubmed]
  19. Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization. Millan, M.J., Cussac, D., Milligan, G., Carr, C., Audinot, V., Gobert, A., Lejeune, F., Rivet, J.M., Brocco, M., Duqueyroix, D., Nicolas, J.P., Boutin, J.A., Newman-Tancredi, A. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  20. Femoral vasodilatation produced by piribedil (ET495) and its metabolite S584 in the hindleg of the dog. Buylaert, W.A. Naunyn Schmiedebergs Arch. Pharmacol. (1977) [Pubmed]
  21. Effect of piribedil and its metabolite, S584, on brain lipid peroxidation in vitro and in vivo. Calzi, F., Bellasio, R., Guiso, G., Caccia, S., Tacconi, M.T. Eur. J. Pharmacol. (1997) [Pubmed]
  22. In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study. Cagnotto, A., Parotti, L., Mennini, T. Eur. J. Pharmacol. (1996) [Pubmed]
  23. Cerebral circulatory and metabolic effects of piribedil. McCulloch, J., Edvinsson, L. Eur. J. Pharmacol. (1980) [Pubmed]
  24. Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: II. Both D2 and "silent" D3 autoreceptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways. Gobert, A., Rivet, J.M., Audinot, V., Cistarelli, L., Spedding, M., Vian, J., Peglion, J.L., Millan, M.J. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  25. Dopaminergic agonist properties of ephedrine--theoretical implications. Angrist, B., Rotrosen, J., Kleinberg, D., Merriam, V., Gershon, S. Psychopharmacology (Berl.) (1977) [Pubmed]
  26. Effect of apomorphine, piribedil and haloperidol on adrenal ornithine decarboxylase activity of the rat. Almazan, G., Ramirez-Gonzalez, M.D., Sourkes, T.L. Neuropharmacology (1982) [Pubmed]
  27. Reduced amounts of S-adenosylmethionine decarboxylase in the adrenal glands of rats following administration of piribedil or 2-deoxyglucose. Ekker, M., Sourkes, T.L., Gabor, R. Biochem. Pharmacol. (1988) [Pubmed]
  28. Role of central dopaminergic mechanisms in piribedil and clonidine induced hypothermia in the rat. Reid, J.L., Lewis, P.J., Myers, M.G. Neuropharmacology (1975) [Pubmed]
  29. Intravenous self-administration of dopamine receptor agonists by rhesus monkeys. Woolverton, W.L., Goldberg, L.I., Ginos, J.Z. J. Pharmacol. Exp. Ther. (1984) [Pubmed]
  30. Involvement of septal and striatal dopamine D-2 receptors in yawning behavior in rats. Yamada, K., Tanaka, M., Shibata, K., Furukawa, T. Psychopharmacology (Berl.) (1986) [Pubmed]
  31. A different balance in the sensitivity of D1 and D2 dopamine receptors accounts for differences in apomorphine-induced hypothermic effects in Swiss and C3H mice. Suaudeau, C., Bousselmame, R., Costentin, J. Neuropharmacology (1992) [Pubmed]
  32. Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. Brocco, M., Dekeyne, A., Papp, M., Millan, M.J. Behavioural pharmacology. (2006) [Pubmed]
  33. Changes of response to dopaminergic drugs in rats submitted to REM-sleep deprivation. Tufik, S. Psychopharmacology (Berl.) (1981) [Pubmed]
  34. Piribedil inhibition of prolactin release induced by mechanical breast emptying in puerperal women. Alagna, S., Lodico, G., Devilla, L., Masala, A., Delitala, G., Rovasio, P.P., Stoppelli, I. Clin. Endocrinol. (Oxf) (1979) [Pubmed]
  35. Differential effects of dopamine agonists and haloperidol on release of prolactin, thyroid stimulating hormone, growth hormone and luteinizing hormone in rats. Mueller, G.P., Simpkins, J., Meites, J., Moore, K.E. Neuroendocrinology (1976) [Pubmed]
  36. Randomized study of the dopamine receptor agonist piribedil in the treatment of mild cognitive impairment. Nagaraja, D., Jayashree, S. The American journal of psychiatry. (2001) [Pubmed]
  37. Amphetamine- type reinforcement by dopaminergic agonists in the rat. Yokel, R.A., Wise, R.A. Psychopharmacology (Berl.) (1978) [Pubmed]
  38. Clinical studies with dopamine-receptor stimulants. Angrist, B., Thompson, H., Shopsin, B., Gershon, S. Psychopharmacologia. (1975) [Pubmed]
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