Skip to main content
SpringerLink
Log in

Methylxanthines During Pregnancy and Early Postnatal Life

  • Chapter
  • First Online:
Methylxanthines

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 200))

Abstract

World-wide, many fetuses and infants are exposed to methylxanthines via maternal consumption of coffee and other beverages containing these substances. Methylxanthines (caffeine, theophylline and aminophylline) are also commonly used as a medication for apnea of prematurity.

The metabolism of methylxanthines is impaired in pregnant women, fetuses and neonates, leading to accumulating levels thereof. Methylxanthines readily passes the placenta barrier and enters all tissues and thus may affect the fetus/newborn at any time during pregnancy or postnatal life, given that the effector systems are mature.

At clinically relevant doses, the major effector system for methylxanthines is adenosine receptors. Animal studies suggest that adenosine receptors in the cardiovascular, respiratory and immune system are developed at birth, but that cerebral adenosine receptors are not fully functional. Furthermore animal studies have shown protective positive effects of methylxanthines in situations of hypoxia/ischemia in neonates. Similarly, a positive long-term effect on lung function and CNS development was found in human preterm infants treated with high doses of caffeine for apneas. There is now evidence that the overall benefits from methylxanthine therapy for apnea of prematurity outweigh potential short-term risks.

On the other hand it is important to note that experimental studies have indicated that long-term effects of caffeine during pregnancy and postnatally may include altered behavior and altered respiratory control in the offspring, although there is currently no human data to support this.

Some epidemiology studies have reported negative effects on pregnancy and perinatal outcomes related to maternal ingestion of high doses of caffeine, but the results are inconclusive. The evidence base for adverse effects of caffeine in first third of pregnancy are stronger than for later parts of pregnancy and there is currently insufficient evidence to advise women to restrict caffeine intake after the first trimester.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 349.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbracchio MP, Camurri A, Ceruti S, Cattabeni F, Falzano L, Giammarioli AM, Jacobson KA, Trincavelli L, Martini C, Malorni W, Fiorentini C (2001) The A3 adenosine receptor induces cytoskeleton rearrangement in human astrocytoma cells via a specific action on rho proteins. Ann N Y Acad Sci 939:63–73

    Article  PubMed  CAS  Google Scholar 

  • Aden U, Herlenius E, Tang LQ, Fredholm BB (2000) Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the rat brain. Pediatr Res 48:177–183

    Article  PubMed  CAS  Google Scholar 

  • Aden U, Leverin AL, Hagberg H, Fredholm BB (2001) Adenosine A(1) receptor agonism in the immature rat brain and heart. Eur J Pharmacol 426:185–192

    Article  PubMed  CAS  Google Scholar 

  • Aldridge A, Bailey J, Neims AH (1981) The disposition of caffeine during and after pregnancy. Semin Perinatol 5:310–314

    PubMed  CAS  Google Scholar 

  • Andersen SL (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26:237–243

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Sitar DS, Parsons WD, Loughnan PM, Neims AH (1976) Pharmacokinetic aspects of theophylline in premature newborns. N Engl J Med 295:413–416

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Gorman W, Bergsteinsson H, Gunn T (1977) Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. J Pediatr 90:467–472

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Collinge JM, Zinman R, Watters G (1979) Maturation of caffeine elimination in infancy. Arch Dis Child 54:946–949

    Article  PubMed  CAS  Google Scholar 

  • Arnaud MJ (1987) The pharmacology of caffeine. Prog Drug Res 31:273–313

    PubMed  CAS  Google Scholar 

  • Back SA, Craig A, Luo NL, Ren J, Akundi RS, Ribeiro I, Rivkees SA (2006) Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Ann Neurol 60:696–705

    Article  PubMed  CAS  Google Scholar 

  • Barr HM, Streissguth AP (1991) Caffeine use during pregnancy and child outcome: a 7-year prospective study. Neurotoxicol Teratol 13:441–448

    Article  PubMed  CAS  Google Scholar 

  • Bauer J, Maier K, Linderkamp O, Hentschel R (2001) Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 107:660–663

    Article  PubMed  CAS  Google Scholar 

  • Bech BH, Obel C, Henriksen TB, Olsen J (2007) Effect of reducing caffeine intake on birth weight and length of gestation: randomised controlled trial. BMJ 334:409

    Article  PubMed  Google Scholar 

  • Bjorklund O, Halldner-Henriksson L, Yang J, Eriksson TM, Jacobson MA, Dare E, Fredholm BB (2008a) Decreased behavioral activation following caffeine, amphetamine and darkness in A3 adenosine receptor knock-out mice. Physiol Behav 95:668–676

    Article  PubMed  Google Scholar 

  • Bjorklund O, Kahlstrom J, Salmi P, Fredholm BB (2008b) Perinatal caffeine, acting on maternal adenosine A(1) receptors, causes long-lasting behavioral changes in mouse offspring. PLoS ONE 3:e3977

    Article  PubMed  Google Scholar 

  • Bodineau L, Saadani-Makki F, Jullien H, Frugiere A (2006) Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats. Respir Physiol Neurobiol 150:94–98

    Article  PubMed  CAS  Google Scholar 

  • Bona E, Aden U, Fredholm BB, Hagberg H (1995) The effect of long term caffeine treatment on hypoxic-ischemic brain damage in the neonate. Pediatr Res 38:312–318

    Article  PubMed  CAS  Google Scholar 

  • Bona E, Aden U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists. Neuropharmacology 36:1327–1338

    Article  PubMed  CAS  Google Scholar 

  • Bracken MB, Triche EW, Belanger K, Hellenbrand K, Leaderer BP (2003a) Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 157:456–466

    Article  PubMed  Google Scholar 

  • Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer BP (2003b) Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies. Obstet Gynecol 102:739–752

    Article  PubMed  Google Scholar 

  • Browne ML (2006) Maternal exposure to caffeine and risk of congenital anomalies: a systematic review. Epidemiology 17:324–331

    Article  PubMed  Google Scholar 

  • CARE Study Group (2008) Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study. BMJ 337:a2332

    Article  Google Scholar 

  • Carnielli VP, Verlato G, Benini F, Rossi K, Cavedagni M, Filippone M, Baraldi E, Zacchello F (2000) Metabolic and respiratory effects of theophylline in the preterm infant. Arch Dis Child Fetal Neonatal Ed 83:F39–F43

    Article  PubMed  CAS  Google Scholar 

  • Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC (2009) Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility. Epidemiology 20:374–381

    Article  PubMed  Google Scholar 

  • Chavez-Valdez R, Wills-Karp M, Ahlawat R, Cristofalo EA, Nathan A, Gauda EB (2009) Caffeine modulates tnf-alpha production by cord blood monocytes: the role of adenosine receptors. Pediatr Res 65:203–208

    Article  PubMed  CAS  Google Scholar 

  • Cnattingius S, Signorello LB, Anneren G, Clausson B, Ekbom A, Ljunger E, Blot WJ, McLaughlin JK, Petersson G, Rane A, Granath F (2000) Caffeine intake and the risk of first-trimester spontaneous abortion. N Engl J Med 343:1839–1845

    Article  PubMed  CAS  Google Scholar 

  • Conde SV, Obeso A, Vicario I, Rigual R, Rocher A, Gonzalez C (2006) Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors. J Neurochem 98:616–628

    Article  PubMed  CAS  Google Scholar 

  • Cook DG, Peacock JL, Feyerabend C, Carey IM, Jarvis MJ, Anderson HR, Bland JM (1996) Relation of caffeine intake and blood caffeine concentrations during pregnancy to fetal growth: prospective population based study. BMJ 313:1358–1362

    Article  PubMed  CAS  Google Scholar 

  • Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ (2004) Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med 200:689–695

    Article  PubMed  CAS  Google Scholar 

  • Dani C, Bertini G, Reali MF, Tronchin M, Wiechmann L, Martelli E, Rubaltelli FF (2000) Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment. Biol Neonate 78:27–32

    Article  PubMed  CAS  Google Scholar 

  • Davi MJ, Sankaran K, Simons KJ, Simons FE, Seshia MM, Rigatto H (1978) Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. J Pediatr 92:91–95

    Article  PubMed  CAS  Google Scholar 

  • Eldridge FL, Millhorn DE, Kiley JP (1985) Antagonism by theophylline of respiratory inhibition induced by adenosine. J Appl Physiol 59:1428–1433

    PubMed  CAS  Google Scholar 

  • Eskenazi B (1999) Caffeine–filtering the facts. N Engl J Med 341:1688–1689

    Article  PubMed  CAS  Google Scholar 

  • Fenster L, Quale C, Hiatt RA, Wilson M, Windham GC, Benowitz NL (1998) Rate of caffeine metabolism and risk of spontaneous abortion. Am J Epidemiol 147:503–510

    Article  PubMed  CAS  Google Scholar 

  • Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    Google Scholar 

  • Fredholm BB (2007) Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ 14:1315–1323

    Article  PubMed  CAS  Google Scholar 

  • Godel JC, Pabst HF, Hodges PE, Johnson KE, Froese GJ, Joffres MR (1992) Smoking and caffeine and alcohol intake during pregnancy in a northern population: effect on fetal growth. CMAJ 147:181–188

    PubMed  CAS  Google Scholar 

  • Grosso LM, Bracken MB (2005) Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy. Ann Epidemiol 15:460–466

    Article  PubMed  Google Scholar 

  • Hammarberg C, Schulte G, Fredholm BB (2003) Evidence for functional adenosine A3 receptors in microglia cells. J Neurochem 86:1051–1054

    Article  PubMed  CAS  Google Scholar 

  • Hart AD, Grimble RF (1990) The effect of methylxanthines on milk volume and composition, and growth of rat pups. Br J Nutr 64:339–350

    Article  PubMed  CAS  Google Scholar 

  • Haskó G, Cronstein B (2010) Methylxanthines and inflammatory cells. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • Henderson MG, McConnaughey MM, McMillen BA (1991) Long-term consequences of prenatal exposure to cocaine or related drugs: effects on rat brain monoaminergic receptors. Brain Res Bull 26:941–945

    Article  PubMed  CAS  Google Scholar 

  • Herlenius E, Aden U, Tang LQ, Lagercrantz H (2002) Perinatal respiratory control and its modulation by adenosine and caffeine in the rat. Pediatr Res 51:4–12

    Article  PubMed  CAS  Google Scholar 

  • Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ (2002) A molecular mechanism of action of theophylline: induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA 99:8921–8926

    Article  PubMed  CAS  Google Scholar 

  • Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Gimenez-Llort L, Escorihuela RM, Fernandez-Teruel A, Wiesenfeld-Hallin Z, Xu XJ, Hardemark A, Betsholtz C, Herlenius E, Fredholm BB (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci USA 98:9407–9412

    Article  PubMed  CAS  Google Scholar 

  • Kalow W, Tang BK (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 50:508–519

    Article  PubMed  CAS  Google Scholar 

  • Khanna NN, Somani SM (1984) Maternal coffee drinking and unusually high concentrations of caffeine in the newborn. J Toxicol Clin Toxicol 22:473–483

    Article  PubMed  CAS  Google Scholar 

  • Kirkinen P, Jouppila P, Koivula A, Vuori J, Puukka M (1983) The effect of caffeine on placental and fetal blood flow in human pregnancy. Am J Obstet Gynecol 147:939–942

    PubMed  CAS  Google Scholar 

  • Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG (1999) Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 341:1639–1644

    Article  PubMed  CAS  Google Scholar 

  • Klebanoff MA, Levine RJ, Clemens JD, Wilkins DG (2002) Maternal serum caffeine metabolites and small-for-gestational age birth. Am J Epidemiol 155:32–37

    Article  PubMed  Google Scholar 

  • Kuzemko JA (1973) Aminophylline in apnoeic attacks of newborn. Lancet 1:1509

    Article  PubMed  CAS  Google Scholar 

  • Lagercrantz H, Yamamoto Y, Fredholm BB, Prabhakar NR, von Euler C (1984) Adenosine analogues depress ventilation in rabbit neonates. Theophylline stimulation of respiration via adenosine receptors? Pediatr Res 18:387–390

    Article  PubMed  CAS  Google Scholar 

  • Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2A receptor. Nature 388:674–678

    Article  PubMed  CAS  Google Scholar 

  • Leinekugel X, Medina I, Khalilov I, Ben-Ari Y, Khazipov R (1997) Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus. Neuron 18:243–255

    Article  PubMed  CAS  Google Scholar 

  • Linnet KM, Wisborg K, Secher NJ, Thomsen PH, Obel C, Dalsgaard S, Henriksen TB (2009) Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: a prospective cohort study. Acta Paediatr 98:173–179

    Article  PubMed  Google Scholar 

  • Marie-Soleil B, Graham TE (2010) Methylxanthines and human health. Epidemiological and experimental evidence. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • McGowan JD, Altman RE, Kanto WP Jr (1988) Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 81:1092–1094

    Article  PubMed  CAS  Google Scholar 

  • McPhee MD, Whiting SJ (1989) The effect of adenosine and adenosine analogues on methylxanthine-induced hypercalciuria in the rat. Can J Physiol Pharmacol 67:1278–1282

    Article  PubMed  CAS  Google Scholar 

  • Millar D, Schmidt B (2004) Controversies surrounding xanthine therapy. Semin Neonatol 9:239–244

    Article  PubMed  Google Scholar 

  • Milsap RL, Krauss AN, Auld PA (1980) Oxygen consumption in apneic premature infants after low-dose theophylline. Clin Pharmacol Ther 28:536–540

    Article  PubMed  CAS  Google Scholar 

  • Momoi N, Tinney JP, Liu LJ, Elshershari H, Hoffmann PJ, Ralphe JC, Keller BB, Tobita K (2008) Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth. Am J Physiol Heart Circ Physiol 294:H2248–H2256

    Article  PubMed  CAS  Google Scholar 

  • Montandon G, Kinkead R, Bairam A (2008) Adenosinergic modulation of respiratory activity: developmental plasticity induced by perinatal caffeine administration. Respir Physiol Neurobiol 164:87–95

    Article  PubMed  CAS  Google Scholar 

  • Müller C, Jacobson KA (2010) Xanthines as adenosine receptor antagonists. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • Nakamoto T, Roy G, Gottschalk SB, Yazdani M, Rossowska M (1991) Lasting effects of early chronic caffeine feeding on rats’ behavior and brain in later life. Physiol Behav 49:721–727

    Article  PubMed  CAS  Google Scholar 

  • Nehlig A, Debry G (1994) Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. Neurotoxicol Teratol 16:531–543

    Article  PubMed  CAS  Google Scholar 

  • Neims AH, von Borstel RW (1983) Caffeine: Metabolism and biochemical mechanisms of action. In: Wurtman RJ, Wurtman JJ (Eds) Nutrition and the Brain, Vol. 6. Raven Press, New York, pp 1–30

    Google Scholar 

  • Ogilvie RI (1978) Clinical pharmacokinetics of theophylline. Clin Pharmacokinet 3:267–293

    Article  PubMed  CAS  Google Scholar 

  • Ohta A, Sitkovsky M (2001) Role of g-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414:916–920

    Article  PubMed  CAS  Google Scholar 

  • Ohta A, Sitkovsky M (2010) Methylxanthines, inflammation and cancer: fundamental mechanisms. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • Rieg T, Steigele H, Schnermann J, Richter K, Osswald H, Vallon V (2005) Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. J Pharmacol Exp Ther 313:403–409

    Article  PubMed  CAS  Google Scholar 

  • Riksen NP, Smits P, Rongen GA (2010) The cardiovascular effects of methylxanthines. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • Rivkees SA (1995) The ontogeny of cardiac and neural A1 adenosine receptor expression in rats. Brain Res Dev Brain Res 89:202–213

    Article  PubMed  CAS  Google Scholar 

  • Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W, Newman RB, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Paul RH, Varner MW, O’Sullivan MJ, Thurnau GR, Conway DL (2004) The relationship of asthma medication use to perinatal outcomes. J Allergy Clin Immunol 113:1040–1045

    Article  PubMed  Google Scholar 

  • Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W (2007) Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 357:1893–1902

    Article  PubMed  CAS  Google Scholar 

  • Stenius-Aarniala B, Riikonen S, Teramo K (1995) Slow-release theophylline in pregnant asthmatics. Chest 107:642–647

    Article  PubMed  CAS  Google Scholar 

  • Tilley SL (2010) Methylxanthines in asthma. In: Fredholm BB (ed) Methylxanthines. Springer, Heidelberg

    Google Scholar 

  • Tsutsumi K, Kotegawa T, Matsuki S, Tanaka Y, Ishii Y, Kodama Y, Kuranari M, Miyakawa I, Nakano S (2001) The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans. Clin Pharmacol Ther 70:121–125

    Article  PubMed  CAS  Google Scholar 

  • Turner CP, Seli M, Ment L, Stewart W, Yan H, Johansson B, Fredholm BB, Blackburn M, Rivkees SA (2003) A1 adenosine receptors mediate hypoxia-induced ventriculomegaly. Proc Natl Acad Sci USA 100:11718–11722

    Article  PubMed  CAS  Google Scholar 

  • Varani K, Portaluppi F, Gessi S, Merighi S, Vincenzi F, Cattabriga E, Dalpiaz A, Bortolotti F, Belardinelli L, Borea PA (2005) Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors. Cell Mol Life Sci 62:2350–2358

    Article  PubMed  CAS  Google Scholar 

  • Vlajinac HD, Petrovic RR, Marinkovic JM, Sipetic SB, Adanja BJ (1997) Effect of caffeine intake during pregnancy on birth weight. Am J Epidemiol 145:335–338

    Article  PubMed  CAS  Google Scholar 

  • Walther FJ, Erickson R, Sims ME (1990) Cardiovascular effects of caffeine therapy in preterm infants. Am J Dis Child 144:1164–1166

    PubMed  CAS  Google Scholar 

  • Wen W, Shu XO, Jacobs DR Jr, Brown JE (2001) The associations of maternal caffeine consumption and nausea with spontaneous abortion. Epidemiology 12:38–42

    Article  PubMed  CAS  Google Scholar 

  • Wisborg K, Kesmodel U, Bech BH, Hedegaard M, Henriksen TB (2003) Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study. BMJ 326:420

    Article  PubMed  Google Scholar 

  • Yang JN, Tiselius C, Dare E, Johansson B, Valen G, Fredholm BB (2007) Sex differences in mouse heart rate and body temperature and in their regulation by adenosine A1 receptors. Acta Physiol (Oxf) 190:63–75

    Article  CAS  Google Scholar 

  • Yurchak AM, Jusko WJ (1976) Theophylline secretion into breast milk. Pediatrics 57:518–520

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Woman and Child Health, Karolinska Institute, 171 77, Stockholm, Sweden

    Ulrika Ådén

Authors
  1. Ulrika Ådén
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulrika Ådén .

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Ådén, U. (2011). Methylxanthines During Pregnancy and Early Postnatal Life. In: Methylxanthines. Handbook of Experimental Pharmacology, vol 200. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13443-2_14

Download citation

Publish with us

Policies and ethics

Search

Navigation