Reserpine

Last updated

Reserpine
Reserpine.svg
Reserpine structure.png
Clinical data
Trade names Serpasil, others
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a601107
License data
Pregnancy
category
  • C
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • Rx-only (banned/discontinued in some countries)
Pharmacokinetic data
Bioavailability 50%
Metabolism gut/liver
Elimination half-life phase 1 = 4.5h,
phase 2 = 271h,
average = 33h
Excretion 62% feces / 8% urine
Identifiers
  • methyl (3β,16β,17α,18β,20α)-11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylate and
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.044 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C33H40N2O9
Molar mass 608.688 g·mol−1
3D model (JSmol)
  • [H][C@]26C[C@@H](OC(=O)c1cc(OC)c(OC)c(OC)c1)[C@H](OC)[C@@H](C(=O)OC)[C@@]2([H])C[C@]5([H])c4[nH]c3cc(OC)ccc3c4CCN5C6
  • InChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m1/s1 Yes check.svgY
  • Key:QEVHRUUCFGRFIF-MDEJGZGSSA-N Yes check.svgY
   (verify)

Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. [1] Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, [2] the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. [3] [4] [5] The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available in 2012. [6]

Contents

The antihypertensive actions of reserpine are largely due to its antinoradrenergic effects, which are a result of its ability to deplete catecholamines (among other monoamine neurotransmitters) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral vascular resistance. [7]

At doses of 0.05 to 0.2 mg per day, reserpine is well tolerated; [8] the most common adverse effect being nasal stuffiness.

Reserpine has also been used for relief of psychotic symptoms. [9] A review found that in persons with schizophrenia, reserpine and chlorpromazine had similar rates of adverse effects, but that reserpine was less effective than chlorpromazine for improving a person's global state. [10]

Medical uses

Reserpine is recommended as an alternative drug for treating hypertension by the JNC 8. [11] A 2016 Cochrane review found reserpine to be as effective as other first-line antihypertensive drugs for lowering of blood pressure. [12] The reserpine–thiazide diuretic combination is one of the few drug treatments shown to reduce mortality in randomized controlled trials: The Hypertension Detection and Follow-up Program, [13] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents, [14] and the Systolic Hypertension in the Elderly Program. [15] Moreover, reserpine was included as a secondary antihypertensive option for patients who did not achieve blood pressure lowering targets in the ALLHAT study. [16]

It was previously used to treat symptoms of dyskinesia in patients with Huntington's disease, [17] but alternative medications are preferred today. [18]

The daily dose of reserpine in antihypertensive treatment is as low as 0.05 to 0.25 mg. The use of reserpine as an antipsychotic drug had been nearly completely abandoned, but more recently it made a comeback as adjunctive treatment, in combination with other antipsychotics, so that more refractory patients get dopamine blockade from the other antipsychotic, and dopamine depletion from reserpine. Doses for this kind of adjunctive goal can be kept low, resulting in better tolerability. Originally, doses of 0.5 mg to 40 mg daily were used to treat psychotic diseases.

Doses in excess of 3 mg daily often required use of an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. For adjunctive treatment, doses are typically kept at or below 0.25 mg twice a day.

Adverse effects

At doses of less than 0.2 mg/day, reserpine has few adverse effects, the most common of which is nasal congestion. [19]

Reserpine can cause: nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration (due to increased cholinergic activity in gastric tissue and impaired mucosal quality), stomach cramps and diarrhea. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose and erectile dysfunction are other consequences of alpha-blockade. [20]

Central nervous system effects at higher doses (0.5 mg or higher) include drowsiness, dizziness, nightmares, Parkinsonism, general weakness and fatigue. [21]

High dose studies in rodents found reserpine to cause fibroadenoma of the breast and malignant tumors of the seminal vesicles among others. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. It may also cause hyperprolactinemia. [20]

Reserpine passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible. [22]

It may produce an excessive decline in blood pressure at doses needed for treatment of anxiety, depression, or psychosis. [23]

Mechanism of action

Reserpine irreversibly blocks the H+-coupled vesicular monoamine transporters, VMAT1 and VMAT2. VMAT1 is mostly expressed in neuroendocrine cells. VMAT2 is mostly expressed in neurons. Thus, it is the blockade of neuronal VMAT2 by reserpine that inhibits uptake and reduces stores of the monoamine neurotransmitters norepinephrine, dopamine, serotonin and histamine in the synaptic vesicles of neurons. [24] VMAT2 normally transports free intracellular norepinephrine, serotonin, and dopamine in the presynaptic nerve terminal into presynaptic vesicles for subsequent release into the synaptic cleft ("exocytosis"). Unprotected neurotransmitters are metabolized by MAO (as well as by COMT), attached to the outer membrane of the mitochondria in the cytosol of the axon terminals, and consequently never excite the post-synaptic cell. Thus, reserpine increases removal of monoamine neurotransmitters from neurons, decreasing the size of the neurotransmitter pools, and thereby decreasing the amplitude of neurotransmitter release. [25] As it may take the body days to weeks to replenish the depleted VMATs, reserpine's effects are long-lasting. [26]

Biosynthetic pathway

Reserpine is one of dozens of indole alkaloids isolated from the plant Rauvolfia serpentina . [27] In the Rauvolfia plant, tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Tryptamine is combined with secologanin in the presence of strictosidine synthetase enzyme and yields strictosidine. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine. [28]

History

Reserpine was isolated in 1952 from the dried root of Rauvolfia serpentina (Indian snakeroot), [29] which had been known as Sarpagandha and had been used for centuries in India for the treatment of insanity, as well as fever and snakebites [30]  — Mahatma Gandhi used it as a tranquilizer. [31] It was first used in the United States by Robert Wallace Wilkins in 1950. Its molecular structure was elucidated in 1953 and natural configuration published in 1955. [32] It was introduced in 1954, two years after chlorpromazine. [33] The first total synthesis was accomplished by R. B. Woodward in 1958. [32]

Reserpine was influential in promoting the thought of a biogenic amine hypothesis of depression. [34] [35] Reserpine-induced depletion of monoamine neurotransmitters in the synapse allegedly caused depression and was cited as evidence that a "chemical imbalance", namely low levels of monoamine neurotransmitters, is what causes clinical depression in humans. A 2003 review showed barely any evidence that reserpine actually causes depression in either human patients or animal models. [36] Notably, reserpine was the first compound ever to be shown to be an effective antidepressant in a randomized placebo-controlled trial. [37] [38] A 2022 systematic review found that studies of the influence of reserpine on mood were highly inconsistent, with similar proportions of studies reporting depressogenic effects, no influence on mood, and antidepressant effects. [39] The quality of evidence was limited, and only a subset of studies were randomized controlled trials. [39] Although reserpine itself cannot provide good evidence for the monoamine hypothesis of depression, other lines of evidence support the idea that boosting serotonin or norepinephrine can effectively treat depression, as shown by SSRIs, SNRIs, and tricyclic antidepressants.

Veterinary use

Reserpine is used as a long-acting tranquilizer to subdue excitable or difficult horses and has been used illicitly for the sedation of show horses, for-sale horses, and in other circumstances where a "quieter" horse might be desired. [40]

It is also used in dart guns.

Research

Animal model of depression and amotivation

Similarly to tetrabenazine, reserpine, via depletion of monoamine neurotransmitters, produces depression-like effects and lack of motivation or fatigue-like symptoms in animals. [41] [42] This can be useful in evaluating new antidepressants and psychostimulant-like agents. [41] [42]

Antibacterial effects

Reserpine inhibits formation of biofilms by Staphylococcus aureus and inhibits the metabolic activity of bacteria present in biofilms. [43]

Related Research Articles

<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers or antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Atenolol</span> Beta blocker medication

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Methyldopa</span> Medication used to treat high blood pressure

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The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles, which release the neurotransmitters into synapses, as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import.

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<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

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<span class="mw-page-title-main">Vesicular monoamine transporter 2</span> Mammalian protein found in Homo sapiens

The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the SLC18A2 gene. SLC18A2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, SLC18A2 function is also necessary for the vesicular release of the neurotransmitter GABA.

<span class="mw-page-title-main">Vesicular monoamine transporter 1</span> Protein-coding gene in the species Homo sapiens

Vesicular monoamine transporter 1 (VMAT1) also known as chromaffin granule amine transporter (CGAT) or solute carrier family 18 member 1 (SLC18A1) is a protein that in humans is encoded by the SLC18A1 gene. VMAT1 is an integral membrane protein, which is embedded in synaptic vesicles and serves to transfer monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin, between the cytosol and synaptic vesicles. SLC18A1 is an isoform of the vesicular monoamine transporter.

<span class="mw-page-title-main">Trace amine</span> Amine receptors in the mammalian brain

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<span class="mw-page-title-main">Reuptake inhibitor</span> Type of drug

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<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

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Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.

<span class="mw-page-title-main">Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial</span>

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<span class="mw-page-title-main">Monoamine-depleting agent</span> Drug class

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References

  1. ↑ Tsioufis C, Thomopoulos C (November 2017). "Combination drug treatment in hypertension". Pharmacological Research. 125 (Pt B): 266–271. doi:10.1016/j.phrs.2017.09.011. PMID   28939201. S2CID   32904492.
  2. ↑ "Reserpine".
  3. ↑ James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. (February 2014). "2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)". JAMA. 311 (5): 507–20. doi:10.1001/jama.2013.284427. PMID   24352797.
  4. ↑ Weir MR (August 2020). "Reserpine: A New Consideration of and Old Drug for Refractory Hypertension". American Journal of Hypertension. 33 (8): 708–710. doi:10.1093/ajh/hpaa069. PMC   7402223 . PMID   32303749.
  5. ↑ Barzilay J, Grimm R, Cushman W, Bertoni AG, Basile J (August 2007). "Getting to goal blood pressure: why reserpine deserves a second look". Journal of Clinical Hypertension. 9 (8): 591–4. doi: 10.1111/j.1524-6175.2007.07229.x . PMC   8110058 . PMID   17673879.
  6. ↑ Wang B, Choudhry NK, Gagne JJ, Landon J, Kesselheim AS (March 2015). "Availability and utilization of cardiovascular fixed-dose combination drugs in the United States". American Heart Journal. 169 (3): 379–386.e1. doi:10.1016/j.ahj.2014.12.014. PMID   25728728.
  7. ↑ Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
  8. ↑ Morley JE (May 2014). "Treatment of hypertension in older persons: what is the evidence?". Drugs & Aging. 31 (5): 331–7. doi:10.1007/s40266-014-0171-7. PMID   24668034. S2CID   207489850.
  9. ↑ Hoenders HJ, Bartels-Velthuis AA, Vollbehr NK, Bruggeman R, Knegtering H, de Jong JT (February 2018). "Natural Medicines for Psychotic Disorders: A Systematic Review". The Journal of Nervous and Mental Disease. 206 (2): 81–101. doi:10.1097/NMD.0000000000000782. PMC   5794244 . PMID   29373456.
  10. ↑ Nur S, Adams CE (April 2016). "Chlorpromazine versus reserpine for schizophrenia". The Cochrane Database of Systematic Reviews. 2016 (4): CD012122. doi:10.1002/14651858.CD012122.pub2. PMC   10350329 . PMID   27124109.
  11. ↑ James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. (February 2014). "2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)". JAMA. 311 (5): 507–20. doi:10.1001/jama.2013.284427. PMID   24352797.
  12. ↑ Shamon SD, Perez MI (December 2016). "Blood pressure-lowering efficacy of reserpine for primary hypertension". The Cochrane Database of Systematic Reviews. 2016 (12): CD007655. doi:10.1002/14651858.CD007655.pub3. PMC   6464022 . PMID   27997978.
  13. ↑ "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group". JAMA. 242 (23): 2562–71. December 1979. doi:10.1001/jama.242.23.2562. PMID   490882. full text at OVID
  14. ↑ "Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg". JAMA. 202 (11): 1028–34. December 1967. doi:10.1001/jama.202.11.1028. PMID   4862069.
  15. ↑ "Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group". JAMA. 265 (24): 3255–64. June 1991. doi:10.1001/jama.265.24.3255. PMID   2046107.
  16. ↑ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (December 2002). "Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)". JAMA. 288 (23): 2981–97. doi: 10.1001/jama.288.23.2981 . PMID   12479763. Archived from the original on November 26, 2009.
  17. ↑ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 11. ISBN   978-1-59541-101-3.
  18. ↑ Thanvi B, Lo N, Robinson T (June 2007). "Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment". Postgraduate Medical Journal. 83 (980): 384–8. doi:10.1136/pgmj.2006.054759. PMC   2600052 . PMID   17551069.
  19. ↑ Curb JD, Schneider K, Taylor JO, Maxwell M, Shulman N (March 1988). "Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program". Hypertension. 11 (3 Pt 2): II51-5. doi: 10.1161/01.hyp.11.3_pt_2.ii51 . PMID   3350594.
  20. 1 2 AJ Giannini, HR Black. Psychiatric, Psychogenic, and Somatopsychic Disorders Handbook. Garden City, NY. Medical Examination Publishing, 1978. Pg. 233. ISBN   0-87488-596-5.
  21. ↑ Barcelos RC, Benvegnú DM, Boufleur N, Pase C, Teixeira AM, Reckziegel P, et al. (February 2011). "Short term dietary fish oil supplementation improves motor deficiencies related to reserpine-induced parkinsonism in rats". Lipids. 46 (2): 143–9. doi:10.1007/s11745-010-3514-0. PMID   21161603. S2CID   4036935.
  22. ↑ kidsgrowth.org Drugs and Other Substances in Breast Milk Archived 2007-06-23 at archive.today Retrieved on June 19, 2009
  23. ↑ Pinel JP (2011). Biopsychology (8th ed.). Boston: Allyn & Bacon. p. 469. ISBN   978-0-205-83256-9.
  24. ↑ Yaffe D, Forrest LR, Schuldiner S (May 2018). "The ins and outs of vesicular monoamine transporters". The Journal of General Physiology. 150 (5): 671–682. doi:10.1085/jgp.201711980. PMC   5940252 . PMID   29666153.
  25. ↑ Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Annals of the New York Academy of Sciences. 1216 (1): 86–98. Bibcode:2011NYASA1216...86E. doi:10.1111/j.1749-6632.2010.05906.x. PMC   4183197 . PMID   21272013.
  26. ↑ German CL, Baladi MG, McFadden LM, Hanson GR, Fleckenstein AE (October 2015). "Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease". Pharmacological Reviews. 67 (4): 1005–24. doi: 10.1124/pr.114.010397 . PMC   4630566 . PMID   26408528.
  27. ↑ "Indole Alkaloids" Archived 2011-09-02 at the Wayback Machine Major Types Of Chemical Compounds In Plants & Animals Part II: Phenolic Compounds, Glycosides & Alkaloids. Wayne's Word: An On-Line Textbook of Natural History. 2005.
  28. ↑ Ramawat et al, 1999.Ramawat KG, Sharma R, Suri SS (2007-01-01). Ramawat KG, Merillon JM (eds.). Medicinal Plants in Biotechnology- Secondary metabolites 2nd edition 2007. Oxford and IBH, India. pp. 66–367. ISBN   978-1-57808-428-9.
  29. ↑ Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
  30. ↑ "Reserpine". The Columbia Encyclopedia (Sixth ed.). Columbia University Press. 2005. Archived from the original on 2009-02-12.
  31. ↑ Pills for Mental Illness?, TIME Magazine , November 8, 1954
  32. 1 2 Nicolaou KC, Sorensen EJ (1996). Classics in Total Synthesis . Weinheim, Germany: VCH. p.  55. ISBN   978-3-527-29284-4.
  33. ↑ López-Muñoz F, Bhatara VS, Alamo C, Cuenca E (2004). "[Historical approach to reserpine discovery and its introduction in psychiatry]". Actas Españolas de Psiquiatría. 32 (6): 387–95. PMID   15529229.
  34. ↑ Everett GM, Toman JE (1959). "Mode of action of Rauwolfia alkaloids and motor activity". Biol Psychiat. 2: 75–81.
  35. ↑ Govindarajulu M (2021). "Reserpine-Induced Depression and Other Neurotoxicity: A Monoaminergic Hypothesis.". In Agrawal D (ed.). Medicinal herbs and fungi : neurotoxicity vs. neuroprotection. Singapore: Springer. ISBN   978-981-334-140-1.
  36. ↑ Baumeister AA, Hawkins MF, Uzelac SM (June 2003). "The myth of reserpine-induced depression: role in the historical development of the monoamine hypothesis". Journal of the History of the Neurosciences. 12 (2): 207–20. doi:10.1076/jhin.12.2.207.15535. PMID   12953623. S2CID   42407412.
  37. ↑ Davies DL, Shepherd M (July 1955). "Reserpine in the treatment of anxious and depressed patients". Lancet. 269 (6881): 117–20. doi:10.1016/s0140-6736(55)92118-8. PMID   14392947.
  38. ↑ Healy, David (1997). The Antidepressant Era. Harvard University Press. ISBN   978-0-674-03958-2.
  39. 1 2 Strawbridge R, Javed RR, Cave J, Jauhar S, Young AH (August 2022). "The effects of reserpine on depression: A systematic review". J Psychopharmacol. 37 (3): 248–260. doi:10.1177/02698811221115762. PMC   10076328 . PMID   36000248. S2CID   251765916.
  40. ↑ Forney B. Reserpine for veterinary use. Available at http://www.wedgewoodpetrx.com/learning-center/professional-monographs/reserpine-for-veterinary-use.html.
  41. 1 2 Stutz PV, Golani LK, Witkin JM (February 2019). "Animal models of fatigue in major depressive disorder". Physiol Behav. 199: 300–305. doi:10.1016/j.physbeh.2018.11.042. PMID   30513290. In a study performed by Sommer et al. (2014), healthy rats treated with the selective dopamine transport (DAT) inhibitor MRZ-9547 (Fig. 1) chose high effort, high reward more often than their untreated matched controls.
  42. 1 2 Salamone JD, Yohn SE, López-Cruz L, San Miguel N, Correa M (May 2016). "Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology". Brain. 139 (Pt 5): 1325–1347. doi:10.1093/brain/aww050. PMC   5839596 . PMID   27189581. Several recent studies have focused on the effort-related effects of [tetrabenazine (TBZ)]. TBZ inhibits VMAT-2 (i.e. vesicular monoamine transporter type 2, encoded by Slc18a2), which results in reduced vesicular storage and depletion of monoamines. The greatest effects of TBZ at low doses have been reported to be on dopamine in the striatal complex, which is substantially depleted relative to norepinephrine and 5- HT (Pettibone et al., 1984; Tanra et al., 1995). Originally developed as a reserpine-type antipsychotic, TBZ has been approved for use as a treatment for Huntington's disease and other movement disorders, but its major side effects include depressive symptoms (Frank, 2009, 2010; Guay, 2010; Chen et al., 2012). Like reserpine, TBZ has been used in studies involving classical animal models of depression (Preskorn et al., 1984; Kent et al., 1986; Wang et al., 2010). Low doses of TBZ that decreased accumbens dopamine release and dopamine-related signal transduction altered effort-related choice behaviour as assessed by concurrent lever pressing/chow feeding choice procedures (Nunes et al., 2013b; Randall et al., 2014).
  43. ↑ Parai D, Banerjee M, Dey P, Mukherjee SK (January 2020). "Reserpine attenuates biofilm formation and virulence of Staphylococcus aureus". Microbial Pathogenesis. 138: 103790. doi:10.1016/j.micpath.2019.103790. PMID   31605761.
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