Chirality of Central Nervous System (CNS) Acting Drugs: A Formidable Therapeutic Hurdle Against CNS Diseases

Author(s): Saganuwan Alhaji Saganuwan*.

Journal Name: Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

Volume 19 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Over fifty percent of drugs being used clinically are chiral and 90% of them are racemates. Unfortunately, they have both adverse and beneficial effects on body systems.

Methods: Because of the erratic effects of chiral compounds on body functional systems, literature search was carried out with a view to identify CNS chiral drugs, their clinical advantages and disadvantages, unique physicochemical properties and structural modifications into safer drugs.

Results: Findings have shown that majority of CNS and non-CNS acting drugs have chiral functional groups that may occur as either dextrorotatory (clockwise) or levorotatory (anticlockwise) or racemates which are inert. Sometimes, the enantiomers (optical isomers) could undergo keto-enol tautomerism, appearing in either acidic or basic or inert form. Chiral CNS acting drugs have agonistic and antagonistic effects, clinical advantages, disadvantages, and special clinical applications, possible modifications for better therapeutic effects and possible synthesis of more potent drugs from racemates. Clockwise chirality may be more effective and safer than the drugs with anticlockwise chirality. When chiral drugs are in racemate state they become inert and may be safer than when they are single. Also, diastereoisomers may be more dangerous than stereoisomers.

Conclusion: Therefore, chiral compounds should be adequately studied in lab rodents and primates, and their mechanisms of actions should be comprehensively understood before being used in clinical setting. Since many of them are toxic, their use should be based on principle of individualized medicine. Their molecular weights, functional groups, metabolites, polymers and stereoisomers could be valuable tools for their modifications.

Keywords: Central nervous system, chirality, depression, excitation, tautomerism, synthetic drugs.

[1]
Nau, C.; Stinchartz, G.R. Drug chirality in anesthetic. Anesthesiology, 2002, 97(497), 502.https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1943881
[2]
Easson, L.H.; Stedman, E. Studies on the relationship between chemical constitution and physiological action: Molecular dissymmetry and physiological activity. Biochem. J., 1933, 27(4), 1257-1266.
[http://dx.doi.org/10.1042/bj0271257] [PMID: 16745220]
[3]
Abood, L.G.; Hoss, W. Stereospecific morphine adsorption to phosphatidyl serine and other membranous components of brain. Eur. J. Pharmacol., 1975, 32(1), 66-75.
[http://dx.doi.org/10.1016/0014-2999(75)90324-6] [PMID: 238865]
[4]
Valenzuela, C.; Snyders, D.J.; Bennett, P.B.; Tamargo, J.; Hondeghem, L.M. Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation, 1995, 92(10), 3014-3024.
[http://dx.doi.org/10.1161/01.CIR.92.10.3014] [PMID: 7586272]
[5]
Schwartz, R.J. Systemic complications of complex regional pain syndrome. Neurosci. Med., 2012, 1-18.
[6]
Parala-Metz, A.; Davis, M. Cancer Pain. Cleveland Clinic., 2005, 1, 1-18.
[7]
Weisberg, L.A.; Garcia, C.; Strab, R. Neurological complication of systemic diseases.In: Essentials of Clinical Neurology; Biller, J.; Ferro, J., Eds.; Elsevier: Amsterdam, 2017, Vol. 120, pp. 1-32.
[8]
Parish, C.R.; Yoshida, C.M. Nutrition intervention for the patient with gastroparesis: An update. Pract. Gastroenterol., 2005, 30, 29-66.
[9]
Behar, J. Physiology and pathophysiology of the biliary tract: The gall bladder and sphincter of Oddi – a review. ISRN Physiol., 2013, 10(8), 37630.
[http://dx.doi.org/10.1155/2013/837630]
[10]
Dietz, I.; Schmitz, A.; Lampey, I.; Schulz, C. Evidence for the use of Levomepromazine for symptom control in the palliative care setting: A systematic review. BMC Palliat. Care, 2013, 12(2), 1-11.
[http://dx.doi.org/10.1186/1472-684X-12-2] [PMID: 23331515]
[11]
Ebert, E. Gastrointestinal involvement in spinal cord injury: A clinical perspective. J. Gastrointestin. Liver Dis., 2012, 21(1), 75-82.
[PMID: 22457863]
[12]
Odom-Forren, J.; Rayens, M.K.; Gokun, Y.; Jalota, L.; Radke, O.; Hooper, V.; Wiggins, A.T.; Apfel, C.C. The relationship of pain and nausea in postoperative patients for 1 week after ambulatory surgery. Clin. J. Pain, 2015, 31(10), 845-851.
[http://dx.doi.org/10.1097/AJP.0000000000000170] [PMID: 25370136]
[13]
Marchettini, P.; Lacerenza, M.; Mauri, E.; Marangoni, C. Painful peripheral neuropathies. Curr. Neuropharmacol., 2006, 4(3), 175-181.
[http://dx.doi.org/10.2174/157015906778019536] [PMID: 18615140]
[14]
Einarson, A.; Maltepe, C.; Boskovic, R.; Koren, G. Treatment of nausea and vomiting in pregnancy: An updated algorithm. Can. Fam. Phys., 2007, 53(12), 2109-2111.
[PMID: 18077743]
[15]
Chapman, T.P.; Hadley, G.; Fratter, C.; Cullen, S.N.; Bax, B.E.; Bain, M.D.; Sapsford, R.A.; Poulton, J.; Travis, S.P. Unexplained gastrointestinal symptoms: Think mitochondrial disease. Dig. Liver Dis., 2014, 46(1), 1-8.
[http://dx.doi.org/10.1016/j.dld.2013.04.008] [PMID: 23768727]
[16]
Mohan, A.; Mohan, A.; Ali, H.M.; Liogier-Weyback, L.; Roberto, A.J.; Kumar, A. The positive correlation between migraine and vertigo: A review. Egypt. J. Otolaryngol., 2016, 32(3), 191-195.
[http://dx.doi.org/10.4103/1012-5574.186525]
[17]
Hill, K.P. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: A clinical review. JAMA, 2015, 313(24), 2474-2483.
[http://dx.doi.org/10.1001/jama.2015.6199] [PMID: 26103031]
[18]
Lobley, R.H.; Swain, A.R. The Role of Food Intolerance, 2015, 521-538.
[19]
Florea, V.G.; Cohn, J.N. The autonomic nervous system and heart failure. Circ. Res., 2014, 114(11), 1815-1826.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.302589] [PMID: 24855204]
[20]
Gulick, E.E.; Namey, M. Bowel dysfunction in persons with multiple sclerosis. Constipat. Caus. Diagn. Treat., 2012, 1, 1-72.
[21]
Warner, D.S.; Warner, M.A. Posteoperative urinary retention, anesthetic and preoperative consideration. Anesthesiology, 2009, 110, 1139-1157.
[http://dx.doi.org/10.1097/ALN.0b013e31819f7aea]
[22]
Fuller-Thomson, E.; Schrumm, M.; Brennenstuhl, S. Migraine and despair factors associated with depression and suicidal ideation among Canadian migraineirs in a population-based study. Depress. Res. Treat., 2013, 2013401487
[http://dx.doi.org/10.1155/2013/401487] [PMID: 24224086]
[23]
Burstein, R.; Noseda, R.; Borsook, D. Migraine: Multiple processes, complex pathophysiology. J. Neurosci., 2015, 35(17), 6619-6629.
[http://dx.doi.org/10.1523/JNEUROSCI.0373-15.2015] [PMID: 25926442]
[24]
Drummond, P.D.; Granston, A. Facial pain increases nausea and headache during motion sickness in migraine sufferers. Brain, 2004, 127(3), 526-534.
[http://dx.doi.org/10.1093/brain/awh061] [PMID: 14749288]
[25]
van Gijn, J.; Rinkel, G.J.E. Subarachnoid haemorrhage: Diagnosis, causes and management. Brain, 2001, 124(2), 249-278.
[http://dx.doi.org/10.1093/brain/124.2.249] [PMID: 11157554]
[26]
Geissliner, G.; Hering, W.; Thomann, P.; Knoll, R.; Kanp, H.D.; Brune, R. Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. Br. J. Anesthes., 1993, 70, 666-671.
[27]
Dickinson, R.; Franks, N.P.; Lieb, W.R. Can the stereoselective effects of the anesthetic isoflurane be accounted for by lipid solubility? Biophys. J., 1994, 66(6), 2019-2023.
[http://dx.doi.org/10.1016/S0006-3495(94)80994-4] [PMID: 7521228]
[28]
Benschop, H.P.; De Jong, L.P.A. Nerve agents stereoisomers: Analysis, isolation and toxicology. Acc. Chem. Res., 1988, 21, 368-374.
[http://dx.doi.org/10.1021/ar00154a003]
[29]
Marris, T.C.; Maynard, P.L.; Sidell, F.R. Chemical Warfare Agents, Toxicology and Treatments, 2nd ed; Wiley & Sons: New York, 2001.
[30]
Sidell, F.R.; Takaful, E.; Franz, D.R. Medical Aspects of Chemical and Biological Warfare: Textbook of Military Medicine, Office of The Surveyor-General; Department of the Army. Office of the Surgeon General: USA, 1997, pp. 129-179.
[http://dx.doi.org/10.21236/ADA398241]
[31]
Brocks, D.R. Anticholinergic drugs used in Parkinson’s disease: An overlooked class of drugs from a pharmacokinetic perspective. J. Pharm. Pharm. Sci., 1999, 2(2), 39-46.https://www.ncbi.nlm.nih.gov/pubmed/10952768
[PMID: 10952768]
[32]
Maboudian-Esfahani, M.; Brocks, D.R. Pharmacokinetics of ethopropazine in the rat after oral and intravenous administration. Biopharm. Drug Dispos., 1999, 20(3), 159-163.
[http://dx.doi.org/10.1002/(SICI)1099-081X(199904)20:3<159:AID-BDD164>3.0.CO;2-D] [PMID: 10211869]
[33]
Onali, P.; Aasen, A.J.; Olianas, M.C. Antagonism by (R)- and (S)-trihexyphenidyl of muscarinic stimulation of adenylyl cyclase in rat olfactory bulb and inhibition in striatum and heart. Br. J. Pharmacol., 1994, 113(3), 775-780.
[http://dx.doi.org/10.1111/j.1476-5381.1994.tb17060.x] [PMID: 7858866]
[34]
Dillane, D.; Finucane, B.T. Local anesthetic systemic toxicity. Can. J. Anaesth., 2010, 57(4), 368-380.
[http://dx.doi.org/10.1007/s12630-010-9275-7] [PMID: 20151342]
[35]
Delfino, R.; Ribein, T.S.; Villar, J.D.F. Organophosphorous compounds as chemical warefare agents: A review. J. Braz. Chem. Soc., 2009, 20(3), 407-428.
[http://dx.doi.org/10.1590/S0103-50532009000300003]
[36]
Saganuwan, S.A. Piroxicam source for synthesis of central nervous system (CNS) acting drugs. Cent. Nerv. Syst. Agents Med. Chem., 2017, 17(2), 135-140.
[http://dx.doi.org/10.2174/1871524916666160719102335] [PMID: 27439371]
[37]
Maher, T.J. Anesthetics: General and local anesthetic Agents; Pharmacodyn. Agents, 2010, pp. 508-539.
[38]
Smith, S.W. Chiral toxicology: It’s the same thing...only different. Toxicol. Sci., 2009, 110(1), 4-30.
[http://dx.doi.org/10.1093/toxsci/kfp097] [PMID: 19414517]
[39]
Harun, N.; Anderson, R.A.; Miller, E.I. Validation of an enzyme-linked immunosorbent assay screening method and a liquid chromatography-tandem mass spectrometry confirmation method for the identification and quantification of ketamine and norketamine in urine samples from Malaysia. J. Anal. Toxicol., 2009, 33(6), 310-321.
[http://dx.doi.org/10.1093/jat/33.6.310] [PMID: 19653934]
[40]
Wille, S.M.R.; Fazio, V.D.; Samyn, N. Drug-facilitated sexual crime by use of ketamine and diazepam by a gynecologist. Drug Test. Analys., 2013. Available at; www.drugtestanalysis.com
[41]
Mika, I.R.; Cumnings, M.R.; Oppenga, R.H. Determination of acepromazine, ketamine, medetomidone and xylazine in serum, multiple residue screening by liquid chromatography-mass spectrometry. J. Anal. Toxicol., 2005, 20, 544-551.
[http://dx.doi.org/10.1093/jat/29.6.544]
[42]
Malaivijitnond, S.; Takenaka, O.; Sankai, T.; Yoshida, T.; Cho, F.; Yoshikawa, Y. Effects of single and multiple injections of ketamine hydrochloride on serum hormone concentrations in male cynomolgus monkeys. Lab. Anim. Sci., 1998, 48(3), 270-274.[https://www.ncbi.nlm.nih.gov/pubmed/10090027]
[PMID: 10090027]
[43]
Eken, C.; Serinken, M.; Dogan, M. Ketamine may be related to reduced ejection fraction in children during the procedural sedation. Hum. Exp. Toxicol., 2017, 36(1), 106-110.
[http://dx.doi.org/10.1177/0960327116637112] [PMID: 26944941]
[44]
Dogaroiu, C.; Sugden, R. Practical implications of GC and HPLC methods for the analysis of drugs of abuse in blood. Rev. Med. Leg., 2008, 16(2), 95-102.
[45]
Dholakia, U.; Clark-Price, S.C.; Keating, S.C.J.; Stern, A.W. Anesthetic effects and body weight changes associated with ketamine-xylazine-lidocaine administered to CD-1 mice. PLoS One, 2017, 12(9) e0184911
[http://dx.doi.org/10.1371/journal.pone.0184911] [PMID: 28910423]
[46]
Dzikiti, T.B. Intravenous anaesthesia in goats: A review. J. S. Afr. Vet. Assoc., 2013, 84(1), E1-E8.
[http://dx.doi.org/10.4102/jsava.v84i1.499] [PMID: 23718851]
[47]
Jud, R.; Picek, S.; Makara, M.A.; Steininger, K.; Hässig, M.; Bettschart-Wolfensberger, R. Comparison of racemic ketamine and S-ketamine as agents for the induction of anaesthesia in goats. Vet. Anaesth. Analg., 2010, 37(6), 511-518.
[http://dx.doi.org/10.1111/j.1467-2995.2010.00570.x] [PMID: 21040375]
[48]
Valverde, A.; Doherty, T.J. Anesthesia and analgesia of ruminants.In: Anesthesia and Analgesia in laboratory Animals, 2nd ed; Academic Press: USA, 2008, pp. 385-411.
[http://dx.doi.org/10.1016/B978-012373898-1.50018-8]
[49]
Galatos, A.D. Anesthesia and analgesia in sheep and goats. Vet. Clin. North Am. Food Anim. Pract., 2011, 27(1), 47-59.
[http://dx.doi.org/10.1016/j.cvfa.2010.10.007] [PMID: 21215889]
[50]
DeRossi, R.; Junqueira, A.L.; Lopes, R.A.; Beretta, M.P. Use of ketamine or lidocaine or in combination for subarachnoid analgesia in goats. Small Rumin. Res., 2005, 59, 95-101.
[http://dx.doi.org/10.1016/j.smallrumres.2004.11.009]
[51]
Waterman, A.E. The pharmacokinetics of ketamine administered intravenously in calves and the modifying effect of premedication with xylazine hydrochloride. J. Vet. Pharmacol. Ther., 1984, 7(2), 125-130.
[http://dx.doi.org/10.1111/j.1365-2885.1984.tb00888.x] [PMID: 6748154]
[52]
Sori, F.; Romgnol, N.; Ferrara, D.; Zaghini, A.; Roncada, P. Plasma and red blood cells concentration profiles of ketamine after single intravenous administration in an anesthetic protocol in horses. Open J. Vet. Med., 2013, 3, 136-142.
[http://dx.doi.org/10.4236/ojvm.2013.32022]
[53]
Valenzuela, C.; Snyder, D.J.; Bennett, P.B.; Tamargo, J.; Hondeghen, L.M. Stereo selective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation, 2005, 92, 304-3024.
[54]
Dillane, D.; Finucane, B.T. Local anesthetic systemic toxicity. Can. J. Anaesth., 2010, 57(4), 368-380.
[http://dx.doi.org/10.1007/s12630-010-9275-7] [PMID: 20151342]
[55]
Fernandes, C.; Oliveira, L.; Tiritan, M.E.; Leitao, L.; Pozzi, A.; Noronha-Matos, J.B.; Correia-de-Sá, P.; Pinto, M.M. Synthesis of new chiral xanthone derivatives acting as nerve conduction blockers in the rat sciatic nerve. Eur. J. Med. Chem., 2012, 55, 1-11.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.049] [PMID: 22819594]
[56]
Tomin, J.; Zivanov-Curlis, J.; Popovic, D.; Glogovac, S.; Basic, D. Differences in local anesthetic effects of optically active isomers of local anesthetic compounds. Biotechnol. Biotechnol. Eq., 2006, 20(3), 9-14.https://www.tandfonline.com/doi/abs/10.1080/13102818.2006.10817373
[57]
Sokolov, V.I. Chirality in the world of stereochemistry. Comput. Math. Appl., 1986, 12(3-4), 547-563.
[http://dx.doi.org/10.1016/0898-1221(86)90410-4]
[58]
Rovillard, R. Flavonoids and flower colour.In: The Flavonoids; Harborne, J.B., Ed.; Springer: Boston, MA, 1988.
[59]
Lien, E.J. Chirality and drug targeting: Pros and cons. J. Drug Target., 1995, 2(6), 527-532.
[http://dx.doi.org/10.3109/10611869509015923] [PMID: 7773615]
[60]
Gerlach, H. Handedness and chirality. Math. Commun. Math. Comp. Chem., 2009, 61, 5-10.
[61]
Mitra, S.; Chopra, P. Chirality and anaesthetic drugs: A review and an update. Indian J. Anaesth., 2011, 55(6), 556-562.
[http://dx.doi.org/10.4103/0019-5049.90608] [PMID: 22223897]
[62]
Hutt, A.J.; Valentova, J. The chiral switch: The development of single enantiomer drugs from racemates. Acta Fac. Pharm. Univ. Comen., 2003, 50, 7-23.
[63]
Buckingham, A.D.; Fischer, P. Optical response of chiral liquid. Chiral. Phys. Chem., 2002, 1, 119-129.
[http://dx.doi.org/10.1021/bk-2002-0810.ch009]
[64]
Testa, B.; Trager, W.F. Racemates versus enantiomers in drug development: Dogmatism or pragmatism? Chirality, 1990, 2(3), 129-133.
[http://dx.doi.org/10.1002/chir.530020302] [PMID: 2252841]
[65]
Islam, M.R.; Mahdi, J.G.; Bowen, I.D. Pharmacological importance of stereochemical resolution of enantiomeric drugs. Drug Saf., 1997, 17(3), 149-165.
[http://dx.doi.org/10.2165/00002018-199717030-00002] [PMID: 9306051]
[66]
Chhabra, N.; Aseri, M.L.; Padmanabhan, D. A review of drug isomerism and its significance. Int. J. Appl. Basic Med. Res., 2013, 3(1), 16-18.
[http://dx.doi.org/10.4103/2229-516X.112233] [PMID: 23776834]
[67]
Caner, H.; Groner, E.; Levy, L.; Agranat, I. Trends in the development of chiral drugs. Drug Discov. Today, 2004, 9(3), 105-110.
[http://dx.doi.org/10.1016/S1359-6446(03)02904-0] [PMID: 15038394]
[68]
Crossley, R. Chirality and the Biological Activity of Drugs, 1st ed; CRC Press: Florida, 1995.
[69]
Yee, G.T. Through the looking glass. J. Chem. Educ., 2000, 79(50), 569-571.
[70]
Cârcu-Dobrin, M.; Budău, M.; Hancu, G.; Gagyi, L.; Rusu, A.; Kelemen, H. Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis. Saudi Pharm. J., 2017, 25(3), 397-403.
[http://dx.doi.org/10.1016/j.jsps.2016.09.007] [PMID: 28344495]
[71]
Leeson, P.D.; St-Gallay, S.A. The influence of the ‘organizational factor’ on compound quality in drug discovery. Nat. Rev. Drug Discov., 2011, 10(10), 749-765.
[http://dx.doi.org/10.1038/nrd3552] [PMID: 21959288]
[72]
Denson, D.D.; Behbehani, M.M.; Gregg, R.V. Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg. Anesth., 1992, 17(6), 311-316.[https://www.ncbi.nlm.nih.gov/pubmed/1286051]
[PMID: 1286051]
[73]
Nguyen, L.A.; He, H.; Pham-Huy, C. Chiral drugs: An overview. Int. J. Biomed. Sci., 2006, 2(2), 85-100.
[PMID: 23674971]
[74]
Rutten, A.J.; Mather, L.E.; McLean, C.F. Cardiovascular effects and regional clearances of i.v. bupivacaine in sheep: Enantiomeric analysis. Br. J. Anaesth., 1991, 67(3), 247-256.
[http://dx.doi.org/10.1093/bja/67.3.247] [PMID: 1911010]
[75]
Rutten, A.J.; Mather, L.E.; McLean, C.F.; Nancarrow, C. Tissue distribution of bupivacaine enantiomers in sheep. Chirality, 1993, 5(7), 485-491.
[http://dx.doi.org/10.1002/chir.530050702] [PMID: 8240923]
[76]
McClure, J.H. Ropivacaine. Br. J. Anaesth., 1996, 76(2), 300-307.
[http://dx.doi.org/10.1093/bja/76.2.300] [PMID: 8777115]
[77]
Lysko, G.S.; Robinson, J.L.; Casto, R.; Ferrone, R.A. The stereospecific effects of isoflurane isomers in vivo. Eur. J. Pharmacol., 1994, 263(1-2), 25-29.
[http://dx.doi.org/10.1016/0014-2999(94)90519-3] [PMID: 7821359]
[78]
Somogy, A.; Bochner, F.; Foster, D. Inside the isomers: The tale of chiral switches. Austal. Prescrib., 2004, 27(2), 47-49.
[79]
Sidebotham, D.A.; Schug, S.A. Stereochemistry in anaesthesia. Clin. Exp. Pharmacol. Physiol., 1997, 24(2), 126-130.
[http://dx.doi.org/10.1111/j.1440-1681.1997.tb01794.x] [PMID: 9075583]
[80]
Aakerman, S.B.A.; Camongs, G.; Sandburg, R.V. Stereoisomerism and differential activity in excitation block by local anesthetics. Trop. J., 1969, 8(3), 337-347.[https://www.ncbi.nlm.nih.gov/pubmed/5370233]
[81]
Markham, A.; Faulds, D. Ropivacaine; A review of its pharmacology and therapeutic use in regional anaesthesia. Drugs, 1996, 52(3), 429-449.
[http://dx.doi.org/10.2165/00003495-199652030-00012] [PMID: 8875132]
[82]
McConathy, J.; Owens, M.J. Sterochemistry in drug action: Primary care companion. J. Clin. Psychol., 2003, 5(2), 70-73.
[83]
Pavan, B.; Dalpiaz, A.; Ciliberti, N.; Biondi, C.; Manfredini, S.; Vertuani, S. Progress in drug delivery to the central nervous system by the prodrug approach. Molecules, 2008, 13(5), 1035-1065.
[http://dx.doi.org/10.3390/molecules13051035] [PMID: 18560328]
[84]
Whiteside, J.B.; Wildsmith, J.A.W. Developments in local anaesthetic drugs. Br. J. Anaesth., 2001, 87(1), 27-35.
[http://dx.doi.org/10.1093/bja/87.1.27] [PMID: 11460810]
[85]
Got, P.A.; Scherrmann, J.M. Stereoselectivity of antibodies for the bioanalysis of chiral drugs. Pharm. Res., 1997, 14(11), 1516-1523.
[http://dx.doi.org/10.1023/A:1012161814494] [PMID: 9434269]
[86]
Ranade, V.V.; Somberg, J.C. Chiral cardiovascular drugs: An overview. Am. J. Ther., 2005, 12(5), 439-459.
[http://dx.doi.org/10.1097/01.mjt.0000167429.37357.0c] [PMID: 16148430]
[87]
Gohel, M.C. Overview on chirality and applications of stereo-selective dissolution testing on the formulation and development work. Dissol. Technol., 2003, 10(3), 16-20.
[88]
Burke, D.; Henderson, D.J. Chirality: A blueprint for the future. Br. J. Anaesth., 2002, 88(4), 563-576.
[http://dx.doi.org/10.1093/bja/88.4.563] [PMID: 12066734]
[89]
Cahn, R.S.; Ingold, C.; Prelog, V. Specification of molecular chirality. Angew. Chem. Int. Engl., 1966, 5, 385-415.
[http://dx.doi.org/10.1002/anie.196603851]
[90]
Pfeiffer, C.C. Optical isomerism and pharmacological action, a generalization. Science, 1956, 124(3210), 29-31.
[http://dx.doi.org/10.1126/science.124.3210.29] [PMID: 13337345]
[91]
Cizmarrikova, R.L.; Koglovsky, J. Pharmacological evaluation of 4-hydroxypropiophenone-potential beta-adreneceptor blockers. Farm. Obz., 1994, 63, 258-260.
[92]
Cizmarikova, R.; Dingora, A.; Kozlovsky, J.; Greksa-Kola, O. Derivatives of parahydroxyacetophenones as novel potential beta-adrenolytic agent. Ceska Slov. Farm., 1990, 39, 403-408.
[PMID: 1982858]
[93]
Cizmarikova, R.; Racanska, T.; Ifrobunova, K.; Lehotay, J.; Misikova, E. Synthesis and enantioseparation and some aryloxyaminopropanol derivatives and their effect on the central nervous system. Act. Facult. Pharm. Univ. Comer., 2003, 50, 38-50.
[94]
Griffith, R.K. Adrenergics and adrenergic blocking agents.In: Burger’s Medicinal Chem and Drug Discovery, 6th ed; Wiley & Sons: New York, 2003, Vol. 6, pp. 1-39.
[http://dx.doi.org/10.1002/0471266949.bmc093]
[95]
Bruchata, K.; Cizmarikova, R. New derivative of aryloxyamino-propanol-structure biological activity relationship. Farm. Obz., 2010, 79, 287-293.
[96]
Hirbec, H.; Gaviria, M.; Vignon, J. Gancyclidine: A new neuroprotective agent acting at the N-methyl-D-aspartate receptor. CNS Drug Rev., 2001, 7(2), 172-198.
[http://dx.doi.org/10.1111/j.1527-3458.2001.tb00194.x] [PMID: 11474423]
[97]
Groban, L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg. Anesth. Pain Med., 2003, 28(1), 3-11.
[http://dx.doi.org/10.1097/00115550-200301000-00002] [PMID: 12567336]
[98]
Indu, H.; Roopa, B.S.; Ponnusankar, S. Intentional chlorpyrifos poisoning in pregnant woman and subsequent fetal death. Int. J. Health Allied Sci., 2016, 5(1), 39-41S.
[http://dx.doi.org/10.4103/2278-344X.173887]
[99]
Johnson, M. Diagnosis and management of hyponatremia. JASN. Am. Soc. Nephrol., 2017, 28(5), 1340-1349.
[100]
Leone, S.; Di Cianni, S.; Casati, A.; Fanelli, G. Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed., 2008, 79(2), 92-105.
[PMID: 18788503]
[101]
Liamis, G.; Milionis, H.J.; Elisaf, M. A review of drug-induced hypernatraemia. NDT Plus, 2009, 2(5), 339-346.
[PMID: 25949338]
[102]
Lien, E.J. Chirality and drug targeting: Pros and cons. J. Drug Target., 1995, 2(6), 527-532.
[http://dx.doi.org/10.3109/10611869509015923] [PMID: 7773615]
[103]
Moorthy, H.K.; Philip, S. TURP syndrome – current concept in the pathophysiology and management. Ind. J. Endocrinol Urol., 2001, 19(2), 97-102.
[104]
Mosti, L.; Menozzi, G.; Fossa, P.; Filippelli, W.; Gessi, S.; Rinaldi, B.; Falcone, G. Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols interesting as potential antiarrhythmic, local anaesthetic and analgesic agents. Arzneimittelforschung, 2000, 50(11), 963-972.
[PMID: 11148862]
[105]
Allen, B.R. Lakhan; Paul, M.; Morns, A.; Lateu, S.; Davies, T.; Scott. G.; Cardiw, M.; Ebedin, M.; Burtin, P.; Stephenson, T.J. Systemic exposure, tolerability and efficacy of pimecrolimus cream 1% in atopic dermatitis patients. Arch. Dis. Child., 2003, 85, 969-973.
[http://dx.doi.org/10.1136/adc.88.11.969] [PMID: 14612358]
[106]
Gal, B.; Bucher, C.; Burns, N.Z. Alkyl halides under explored motifs in medicine. Mar. Drugs, 2016, 14, 1-11.
[http://dx.doi.org/10.3390/md14110206]
[107]
Sheldon, R.A. Chirotechnology, industrial synthesis of optically active compounds. J. Chem. Educ., 1993, 71(1), A23.
[108]
Stegman, J.K. Stedman’s Medical Dictionary; , 2006.
[109]
Matsunaga, K.; Nakamura, K.; Veda, M. Intrinsic beta-sympathetic activity of dilevalol, R-isomer of labetalol. J.Pharm. Dyn, 1985, 8(9), 785-787.
[110]
Di, L.; Kerns, E.H. Stereochemical conversion. In: Comprehensive Medicinal Chemistry 11, 2nd ed; Elsevier Science: Amsterdam, 2007, p. 7200.
[111]
Saganuwan, S.A. In vivo piroxicam metabolites: Possible synthesis for source of central nervous system (CNS) acting drugs. Cent. Nervous. Syst. Agents Med. Chem., 2017, 17(3), 178-186.
[http://dx.doi.org/10.2174/1871524917666161111093759]
[112]
Saganuwan, S.A. Biomedical application of polymers: A case study of non-CNS drugs becoming CNS acting drugs. Cent. Nervous. Syst. Agents Med. Chem., 2018, 18(1), 32-38.
[http://dx.doi.org/10.2174/1871524917666170821115748] [PMID: 28828968]
[113]
Brooks, W.H.; Guida, W.C.; Daniel, K.G. The significance of chirality in drug design and development. Curr. Top. Med. Chem., 2011, 11(7), 760-770.
[http://dx.doi.org/10.2174/156802611795165098] [PMID: 21291399]
[114]
Simon, M.J.G.; Veering, B.T. Factors affecting the pharmacokinetics and neural block characteristics after epidural administration of local anesthetics. Eur. J. Pain, 2010, 4(4), 209-218.
[http://dx.doi.org/10.1016/j.eujps.2010.09.018]
[115]
Cusato, M.; Niebel, T.; Bettinelli, S.; Regazzi, M. How pharmacokinetic can help to choose the right local anesthetics during epidural infusion. Eur. J. Pain, 2011, 5(2), 471-475.
[http://dx.doi.org/10.1016/j.eujps.2011.08.003]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 3
Year: 2019
Page: [171 - 179]
Pages: 9
DOI: 10.2174/1871524919666190624150214
Price: $58

Article Metrics

PDF: 28
HTML: 2
EPUB: 3
PRC: 1

Special-new-year-discount