Summary: Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the ADRENERGIC ANTAGONISTS and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals (see ADRENERGIC AGENTS). Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists, see ADRENERGIC ALPHA-AGONISTS) are included here.

Top Publications

  1. Hofer S, Steppan J, Wagner T, Funke B, Lichtenstern C, Martin E, et al. Central sympatholytics prolong survival in experimental sepsis. Crit Care. 2009;13:R11 pubmed publisher
    ..By down-regulating pro-inflammatory mediators sympatholytics may be a useful adjunct sedative in patients with a high risk for developing sepsis.
  2. Demas G, Bartness T. Novel method for localized, functional sympathetic nervous system denervation of peripheral tissue using guanethidine. J Neurosci Methods. 2001;112:21-8 pubmed
    ..Collectively, these results suggest that locally applied, chemical sympathectomy with guanethidine provides an effective, restricted method for sympathectomizing WAT, spleen and likely other peripheral tissues. ..
  3. Cicchetti F, Brownell A, Williams K, Chen Y, Livni E, Isacson O. Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci. 2002;15:991-8 pubmed
    ..These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging. ..
  4. Deumens R, Blokland A, Prickaerts J. Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol. 2002;175:303-17 pubmed
    ..The choice of the behavioral parameters determines the use of unilateral or bilateral lesions, although it is obvious that the bilateral model mimics the human situation more closely. ..
  5. Rooks C, Penn D, Kelso E, Bowers R, Bartness T, Harris R. Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin. Am J Physiol Regul Integr Comp Physiol. 2005;289:R92-102 pubmed
    ..These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots...
  6. He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 2001;909:187-93 pubmed
    ..All these results suggest that microglial activation may be involved in the nigral cell degeneration in 6-OHDA induced parkinsonian mice. ..
  7. Yoon M, Shin M, Kim T, Kim B, Ko I, Sung Y, et al. Treadmill exercise suppresses nigrostriatal dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson's rats. Neurosci Lett. 2007;423:12-7 pubmed
    ..The results of the present study show that treadmill exercise may provide therapeutic value for the treatment of Parkinson's disease patients. ..
  8. Rose S, Ramsay Croft N, Jenner P. The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of l-dopa in unilaterally 6-OHDA-lesioned rats. Brain Res. 2007;1133:110-4 pubmed
    ..ST1535 may be useful in the treatment of Parkinson's disease and effective in reducing the use of l-dopa. ..
  9. Topka H. [Diagnosis and treatment of tics]. MMW Fortschr Med. 2007;149 Suppl 2:4-7; quiz 8 pubmed
    ..For chronic tics and for pronounced symptoms, drug therapy with neuroleptic drugs or clonidine is a possibility. However, the efficacy of these substances is limited. ..

More Information


  1. Costa C, Sgobio C, Siliquini S, Tozzi A, Tantucci M, Ghiglieri V, et al. Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease. Brain. 2012;135:1884-99 pubmed publisher
  2. Ngampramuan S, Baumert M, Beig M, Kotchabhakdi N, Nalivaiko E. Activation of 5-HT(1A) receptors attenuates tachycardia induced by restraint stress in rats. Am J Physiol Regul Integr Comp Physiol. 2008;294:R132-41 pubmed
    ..Activation of central 5-HT(1A) receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area. ..
  3. Niu X, Canlon B. The signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea. Neuroscience. 2006;137:981-90 pubmed
    ..One signal transduction pathway of D1 receptor in the auditory nerve is via protein kinase A-mediated glutamate receptor 1 phosphorylation. ..
  4. Grădinaru I, Ghiciuc C, Nechifor M, Dumitriu G, Doloca A. [Research on the effect of atenolol on lidocaine pharmacokinetics in rats]. Rev Med Chir Soc Med Nat Iasi. 2006;110:687-91 pubmed
    ..23 +/- 6.59 ng/ml x min vs. 190.71 +/- 19.75 ng/ml x min). Tmax was 20 minutes, similar for both groups. local anesthesia with lidocaine might be enhanced in the presence of atenolol compared to controls. ..
  5. Allred R, Adkins D, Woodlee M, Husbands L, Maldonado M, Kane J, et al. The vermicelli handling test: a simple quantitative measure of dexterous forepaw function in rats. J Neurosci Methods. 2008;170:229-44 pubmed publisher
    ..Because of its ease of administration and sensitivity to lateralized impairments in skilled forepaw use, this measure may be useful in rat models of upper extremity impairment. ..
  6. Monville C, Torres E, Pekarik V, Lane E, Dunnett S. Genetic, temporal and diurnal influences on L-dopa-induced dyskinesia in the 6-OHDA model. Brain Res Bull. 2009;78:248-53 pubmed publisher
    ..We conclude that a complex combination of individual factors are likely to interact to regulate the onset and development of abnormal movements in some animals but not others. ..
  7. Ziegler M, Milic M, Sun P. Antihypertensive therapy for patients with obstructive sleep apnea. Curr Opin Nephrol Hypertens. 2011;20:50-5 pubmed publisher
    ..It is reasonable to prescribe shorter acting antihypertensive drugs at night to treat nocturnal hypertension. ..
  8. Chao O, Pum M, Huston J. The interaction between the dopaminergic forebrain projections and the medial prefrontal cortex is critical for memory of objects: implications for Parkinson's disease. Exp Neurol. 2013;247:373-82 pubmed publisher
    ..Thus, the interaction between the dopaminergic forebrain projections, particularly the nigrostriatal dopamine, and the medial prefrontal cortex is critical for object recognition memory but not for spatial working memory in rats. ..
  9. de Pablos R, Herrera A, Tomás Camardiel M, Machado A, Cano J. Deprenyl enhances the striatal neuronal damage produced by quinolinic acid. Brain Res Mol Brain Res. 2005;141:48-57 pubmed
    ..All these data justify why deprenyl worsen some pathological signals of disorders involving excitotoxicity. This also may be involved in other secondary effects described for deprenyl. ..
  10. Ridley R, Cummings R, Leow Dyke A, Baker H. Neglect of memory after dopaminergic lesions in monkeys. Behav Brain Res. 2006;166:253-62 pubmed
    ..Failure to self-initiate retrieval of relevant knowledge may contribute to the paucity of cognitive style and loss of executive skills exhibited by some patients with Parkinson's disease. ..
  11. Heuer A, Lelos M, Kelly C, Torres E, Dunnett S. Dopamine-rich grafts alleviate deficits in contralateral response space induced by extensive dopamine depletion in rats. Exp Neurol. 2013;247:485-95 pubmed publisher
  12. Brignole Baudouin F, Riancho L, Liang H, Nakib Z, Baudouin C. In vitro comparative toxicology of polyquad-preserved and benzalkonium chloride-preserved travoprost/timolol fixed combination and latanoprost/timolol fixed combination. J Ocul Pharmacol Ther. 2011;27:273-80 pubmed publisher
    ..5% fixed combination ophthalmic solution (travoprost/timolol BAK), (2) commercially available latanoprost 0.005%/timolol 0.5% fixed combination ophthalmic solution (latanoprost/timolol BAK), and (3) their associated BAK concentrations...
  13. Stewart D, Waxman K. Management of postoperative ileus. Am J Ther. 2007;14:561-6 pubmed
    ..The literature on early refeeding, gum chewing, and the use of tube feeds is reviewed. In addition, new and experimental drugs currently in development are discussed. ..
  14. Sun J, Gao Y, Yang L, Li Z, Lu G, Yew D. Neural-tube-derived neuroepithelial stem cells: a new transplant resource for Parkinson's disease. Neuroreport. 2007;18:543-7 pubmed
    ..Our results demonstrate that neuroepithelial cells may be a new source of donor material for Parkinson's disease. ..
  15. Torres E, Monville C, Lowenstein P, Castro M, Dunnett S. Delivery of sonic hedgehog or glial derived neurotrophic factor to dopamine-rich grafts in a rat model of Parkinson's disease using adenoviral vectors Increased yield of dopamine cells is dependent on embryonic donor age. Brain Res Bull. 2005;68:31-41 pubmed
  16. Vagts D, Iber T, Roesner J, Mutz C, Kurzweg V, Harkner C, et al. Effects of systemically applied clonidine on intestinal perfusion and oxygenation in healthy pigs during general anaesthesia and laparotomy. Eur J Anaesthesiol. 2005;22:879-86 pubmed
    ..However, regional macrohaemodynamic perfusion was maintained and intestinal oxygenation did not change. Clonidine does not impair intestinal mucosal and serosal oxygenation under physiological conditions. ..
  17. Kabuto H, Nishizawa M, Tada M, Higashio C, Shishibori T, Kohno M. Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopamine depression in mouse striatum and increases superoxide scavenging activity in serum. Neurochem Res. 2005;30:325-32 pubmed
    ..Effects of zingerone treatment in this model suggest possible value in treatment of Parkinson's disease. ..
  18. Swerdlow N, Shoemaker J, Kuczenski R, Bongiovanni M, Neary A, Tochen L, et al. Forebrain D1 function and sensorimotor gating in rats: effects of D1 blockade, frontal lesions and dopamine denervation. Neurosci Lett. 2006;402:40-5 pubmed
    ..The effects of systemic SCH23390 were not opposed by NAC DA depletion. D1 receptors regulate PPI in rats, but this effect does not appear to be mediated either by the MPFC or by increased mesolimbic DA activity. ..
  19. Skurikhin E, Khmelevskaya E, Pershina O, Andreeva T, Ermolaeva L, Krupin V, et al. Mechanisms of the anti-inflammatory and antifibrotic activity of a sympatholytic agent during toxic pulmonary fibrosis. Bull Exp Biol Med. 2012;153:638-43 pubmed
    ..The antifibrotic effect of reserpine was due to a decrease in the number of committed precursors for mesenchymopoiesis. ..
  20. Fleming S, Schallert T, Ciucci M. Cranial and related sensorimotor impairments in rodent models of Parkinson's disease. Behav Brain Res. 2012;231:317-22 pubmed publisher
    ..Here we describe useful novel and established behavioral outcome measures for assessing limb and cranial sensorimotor functions in toxin and genetic models of parkinsonism in rats and mice. ..
  21. Siddiqi L, Joles J, Oey P, Blankestijn P. Atorvastatin reduces sympathetic activity in patients with chronic kidney disease. J Hypertens. 2011;29:2176-80 pubmed publisher
    ..Atorvastatin reduced total and low-density lipoprotein cholesterol. Atorvastatin has a further sympatholytic effect in CKD patients, who are on chronic aliskiren, which is independent of blood pressure and heart rate. ..
  22. Xavier L, Viola G, Ferraz A, Da Cunha C, Deonizio J, Netto C, et al. A simple and fast densitometric method for the analysis of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area. Brain Res Brain Res Protoc. 2005;16:58-64 pubmed
    ..We believe that this protocol will facilitate the evaluation of mesencephalic TH immunoreactivity in various available animal models of Parkinson's disease. ..
  23. Monville C, Torres E, Dunnett S. Validation of the l-dopa-induced dyskinesia in the 6-OHDA model and evaluation of the effects of selective dopamine receptor agonists and antagonists. Brain Res Bull. 2005;68:16-23 pubmed
    ..g. using grafts while blocking the unwanted adverse effects of the drugs. ..
  24. Castiglioni P, Parati G, Di Rienzo M, Carabalona R, Cividjian A, Quintin L. Scale exponents of blood pressure and heart rate during autonomic blockade as assessed by detrended fluctuation analysis. J Physiol. 2011;589:355-69 pubmed publisher
    ..Results are explained by different distribution and dynamics of acetylcholine receptors and of ?- and ?-adrenergic receptors between heart and vasculature. ..
  25. Paille V, Picconi B, Bagetta V, Ghiglieri V, Sgobio C, Di Filippo M, et al. Distinct levels of dopamine denervation differentially alter striatal synaptic plasticity and NMDA receptor subunit composition. J Neurosci. 2010;30:14182-93 pubmed publisher
    ..The use of the TAT2A cell-permeable peptide, as an innovative therapeutic strategy in early PD, rescues physiological NMDA receptor composition, synaptic plasticity, and motor behavior. ..
  26. Klein R, Alvarez Jimenez R, Sukhai R, Oostdijk W, Bakker B, Reeser H, et al. Pharmacokinetics and pharmacodynamics of orally administered clonidine: a model-based approach. Horm Res Paediatr. 2013;79:300-9 pubmed publisher
    ..Clonidine concentrations during the test were higher than necessary according to model-based predictions. A lower clonidine dose may be sufficient and may produce fewer side effects. ..
  27. Cauli O, Pinna A, Morelli M. Subchronic intermittent caffeine administration to unilaterally 6-hydroxydopamine-lesioned rats sensitizes turning behaviour in response to dopamine D(1) but not D(2) receptor agonists. Behav Pharmacol. 2005;16:621-6 pubmed
    ..The results show that repeated intermittent caffeine exposure enhances the motor stimulant effects elicited by dopamine agonists by a preferential sensitization of dopamine D(1) receptors. ..
  28. Wachter B, Schürger S, Schmid A, Gröger A, Sadler R, Speidel A, et al. 6-Hydroxydopamine leads to T2 hyperintensity, decreased claudin-3 immunoreactivity and altered aquaporin 4 expression in the striatum. Behav Brain Res. 2012;232:148-58 pubmed publisher
    ..g. behavioral alterations). Therefore, when using 6-OHDA in Parkinson's models effects that are not mediated by degeneration of catecholaminergic neurons have to be considered. ..
  29. Li C, Huang G, Sui Z, Han E, Chung Y. Effects of 6-hydroxydopamine lesioning of the medial prefrontal cortex on social interactions in adolescent and adult rats. Brain Res. 2010;1346:183-9 pubmed publisher
    ..Further research is warranted to investigate the mechanisms underpinning the detrimental effects of 6-OHDA lesioning of the mPFC on social behaviors. ..
  30. Eckart M, Huelse Matia M, McDonald R, Schwarting R. 6-hydroxydopamine lesions in the rat neostriatum impair sequential learning in a serial reaction time task. Neurotox Res. 2010;17:287-98 pubmed publisher
    ..Furthermore,and most importantly, they suggest that dopaminergic-striatal networks also play an important role in sequential behavior, especially its acquisition. ..
  31. Santini E, Alcacer C, Cacciatore S, Heiman M, Herve D, Greengard P, et al. L-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. J Neurochem. 2009;108:621-33 pubmed publisher
    ..Our results demonstrate that in the dopamine-depleted striatum, L-DOPA activates ERK signaling specifically in striatonigral MSNs. This regulation may result in ERK-dependent changes in striatal plasticity leading to dyskinesia...
  32. Chalovich E, Zhu J, Caltagarone J, Bowser R, Chu C. Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J Biol Chem. 2006;281:17870-81 pubmed
  33. Malagelada C, Jin Z, Greene L. RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting Akt phosphorylation/activation. J Neurosci. 2008;28:14363-71 pubmed publisher
    ..These observations support a sequential mechanism in which PD-associated stresses induce RTP801, suppress mTOR signaling, deplete phosphorylated/activated Akt and permit neuron degeneration and death. ..
  34. Santos J, Cunha J, Dierschnabel A, Campêlo C, Leão A, Silva A, et al. Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine. Behav Brain Res. 2013;253:68-77 pubmed publisher
  35. Drummond P. Immersion of the hand in ice water releases adrenergic vasoconstrictor tone in the ipsilateral temple. Auton Neurosci. 2006;128:70-5 pubmed
    ..Instead, they suggest that the sympathetic nervous system is highly differentiated, with separate control of discrete reflex pathways on each side of the body. ..
  36. Hyatt Sachs H, Schreiber R, Shoemaker S, Sabe A, Reed E, Zigmond R. Activating transcription factor 3 induction in sympathetic neurons after axotomy: response to decreased neurotrophin availability. Neuroscience. 2007;150:887-97 pubmed
  37. Gold S, Hoang C, Potts B, Porras G, Pioli E, Kim K, et al. RGS9-2 negatively modulates L-3,4-dihydroxyphenylalanine-induced dyskinesia in experimental Parkinson's disease. J Neurosci. 2007;27:14338-48 pubmed
    ..However, the findings also suggest that increasing RGS9-2 expression and/or function in PD patients may only be a suitable therapeutic strategy to control involuntary movements induced by nonselective DA agonist such as L-dopa...
  38. Kacem K, Sercombe R. Differing influence of sympathectomy on smooth muscle cells and fibroblasts in cerebral and peripheral muscular arteries. Auton Neurosci. 2006;124:38-48 pubmed
  39. Yoon S, Kwon Y, Kim H, Roh D, Seo H, Han H, et al. Peripheral bee venom's anti-inflammatory effect involves activation of the coeruleospinal pathway and sympathetic preganglionic neurons. Neurosci Res. 2007;59:51-9 pubmed
    ..These results indicate that BV-induced activation of the contralateral LC-descending noradrenergic pathway increased the activity of SPNs that project to the adrenal medulla and this pathway is necessary for BVAI. ..
  40. Gittis A, Hang G, LADOW E, Shoenfeld L, Atallah B, Finkbeiner S, et al. Rapid target-specific remodeling of fast-spiking inhibitory circuits after loss of dopamine. Neuron. 2011;71:858-68 pubmed publisher
  41. Xhaet O, Argacha J, Pathak A, Gujic M, Houssiere A, Najem B, et al. Sympathoexcitation increases the QT/RR slope in healthy men: differential effects of hypoxia, dobutamine, and phenylephrine. J Cardiovasc Electrophysiol. 2008;19:178-84 pubmed
    ..Vagal cardiac activation by phenylephrine does not change the QT slopes. This reveals that the sympathetic system is an important determinant of QT/RR dynamicity in healthy men. ..
  42. Tuon T, Valvassori S, Lopes Borges J, Luciano T, Trom C, Silva L, et al. Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson's disease. Neuroscience. 2012;227:305-12 pubmed publisher
    ..The effects of exercise on PD indicate the possibility that exercise, to a certain extent, modulates neurochemical status in the striatum of rats, possibly by improving the oxidative stress parameters. ..
  43. Sarkaki A, Badavi M, Hoseiny N, Gharibnaseri M, Rahim F. Postmenopausal effects of intrastriatal estrogen on catalepsy and pallidal electroencephalogram in an animal model of Parkinson's disease. Neuroscience. 2008;154:940-5 pubmed publisher
  44. Simola N, Tronci E, Pinna A, Morelli M. Subchronic-intermittent caffeine amplifies the motor effects of amphetamine in rats. Amino Acids. 2006;31:359-63 pubmed
    ..These results suggest that subchronic caffeine treatment results in an enhancement of its motor stimulant effects, rather than in tolerance, and induces neuroadaptive facilitatory changes in dopamine transmission. ..
  45. Barlow M, Deo S, Johnson S, Caffrey J. Vagotonic effects of enkephalin are not mediated by sympatholytic mechanisms. Exp Biol Med (Maywood). 2006;231:387-95 pubmed
    ..Furthermore, the sympatholytic effect is mediated independently by kappa-receptors. The sympatholytic effect of sustained kappa-receptor stimulation appears to evolve gradually into a functional state not easily reversed. ..
  46. Furuta A, Suzuki Y, Asano K, de Groat W, Egawa S, Yoshimura N. Urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury in female rats. Int Urogynecol J. 2011;22:963-70 pubmed publisher
    ..These results suggest that ?(1)-adrenoceptor and muscarinic receptor-mediated contractility is upregulated in the proximal urethra 4 weeks after PNT. ..
  47. Ferreira N, Mitkovski M, Stuhmer W, Pardo L, Del Bel E. Ether-à-go-go 1 (Eag1) potassium channel expression in dopaminergic neurons of basal ganglia is modulated by 6-hydroxydopamine lesion. Neurotox Res. 2012;21:317-33 pubmed publisher
    ..The Eag1-K(+) channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons. ..
  48. Chen X, Tagliaferro P, Kareva T, Yarygina O, Kholodilov N, Burke R. Neurotrophic effects of serum- and glucocorticoid-inducible kinase on adult murine mesencephalic dopamine neurons. J Neurosci. 2012;32:11299-308 pubmed publisher
    ..It therefore offers a novel target for therapeutic development. ..
  49. Koprich J, Reske Nielsen C, Mithal P, Isacson O. Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. J Neuroinflammation. 2008;5:8 pubmed publisher
    ..These data provide insight into the etiology of PD and support a role for inflammation as a risk factor for the development of neurodegenerative disease. ..
  50. Lev N, Ickowicz D, Melamed E, Offen D. Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology. 2008;29:397-405 pubmed publisher
    ..These results may imply that DJ-1 plays an important role in the neuronal defense mechanism against oxidative insults. ..
  51. Zhang X, Andren P, Chergui K, Svenningsson P. Neurokinin B/NK3 receptors exert feedback inhibition on L-DOPA actions in the 6-OHDA lesion rat model of Parkinson's disease. Neuropharmacology. 2008;54:1143-52 pubmed publisher
    ..The inhibitory influence of NKB/NK(3)R on dopamine transmission dominates in an animal model of PD and provides a feedback inhibition on actions mediated via L-DOPA. ..
  52. Saade N, Farhat O, Rahal O, Safieh Garabedian B, Le Bars D, Jabbur S. Ultra violet-induced localized inflammatory hyperalgesia in awake rats and the role of sensory and sympathetic innervation of the skin. Brain Behav Immun. 2008;22:245-56 pubmed