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Brief Communication
Abstract
Isomerism finds its importance in the field of clinical pharmacology and pharmacotherapeutics, as isomers differ in their
pharmacokinetic and pharmacodyanmic properties. Drug isomerism has opened a new era of drug development. Currently,
knowledge of isomerism has helped us in introducing safer and more effective drug alternatives of the newer as well as
existing drugs. Many existing drugs have gone chiral switch i.e., switching from racemic mixture to one of its isomers.
Cetrizine to levocetrizine is one of such examples, where effective and safer drug has been made available. In this article, we
have attempted to review the basic concepts of stereochemistry and chirality and their significance in pharmacotherapeutics.
Various pharmacological aspects such as pharmacokinetic and pharmacodynamic variations resulting out of chirality has been
discussed in detail in this article.
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with different orientation of atoms in the space.These different solubities, etc. But the important difference between two
orientations cannot interconvert freely by bond rotation. is that each member rotates the plane of polarized light to
Example is dand samphetamine. Conformational isomers are the same degree, in opposite directions. Isomerization or
different by relative spatial arrangements of atoms that results enantiomerization is the conversion of one stereoisomeric
from rotation about sigma bonds.Thus, unlike configurational form into another (Ribuprofen to Sibuprofen). When
isomers, conformers are interconverting stereoisomers of a isomerization occurs by the change of configuration at a single
single compound. chiral center, the process is called epimeriztion, and when it
leads to the formation of racemes, it is termed racemization.[3]
Several Neurologic Diseases
Results from Altered Protein Drug Isomerism and Chirality
Conformation
Stereoisomers differ in pharmacokinetic and pharmacodynamic
Prions diseases properties. Pharmacokinetic differences resulting out of
Prion diseases are fatal neurodegenerative diseases stereoisomerism can be in absorption like LMethotrexate
characterized by spongiform changes, astrocytic gliomas, and is better absorbed than DMethotrexate, Esomeprazole is
neuronal loss resulting from the deposition of insoluble protein more bioavailable than racemic omeprazole; in distribution
aggregates in neural cells. They include CreutzfeldtJakob like SWarfarin is more extensively bound to albumin than
disease in humans, scrapie in sheep, and bovine spongiform RWarfarin, hence it has lower volume of distribution.[5,9]
encephalopathy in cattle.[3] Levocetrizine has smaller volume of distribution than its
dextroisomer,[10] dPropranolol is more extensively bound to
Alzheimers disease proteins than lPropranolol; in metabolism like SWarfarin is
Refolding or misfolding of protein endogenous to human brain more potent and metabolized by ring oxidation while RWarfarin
tissue, amyloid beta or Abetaamyloid, is a prominent feature is less potent and metabolized by side chain reduction, half life
of Alzheimers disease. In Alzheimers disease patients, levels of SWarfarin is 32 hours while it is 54hours for RWarfarin.[5,9]
of Abetaamyloid/amyloid beta or become elevated, and this
protein undergoes a conformational transformation from a Pharmacodynamic differences resulting out of stereoisomerism
soluble helixrich state to a state rich in Abeta or amyloid beta can be in pharmacological activity and potency like lPropranolol
sheet and prone to selfaggregation.[3] has betaadrenoceptors blocking action while dpropranolol
is inactive; Carvedilol is a racemic mixture, the S() isomer
Chirality is a nonselective betaadrenoceptor blocker, while both S()
and R(+) isomers have approximately equally alphablocking
A molecule is referred to as chiral if it is not super imposable potency; STimolol is more potent alphablocker than Rtimolol
to its mirror image. The best example of chirality is our but both are equipotent ocular hypotensive agents; Labetalol
hand. Two hands cannot be superimposed identically, despite is formulated as a racemic mixture of four isomers, two of
the fact that our fingers of each hand are connected in the these isomers the (S, S) and (R, S) isomer are relatively
same way. The term chiral was derived from Greek word inactive, a third(S, R)is a potent alphablocker and the fourth
cheir meaning hand and was applied as a description of one(R, R)is a potent betablocker. Labetalol has a 3:1 ratio
left and right handedness of crystal structure resulting from of beta:Alpha antagonism after oral administration; Sotalol is
molecular asymmetry.[6] An atom such as carbon, nitrogen, formulated as a racemic mixture of Dand Lisomers, Lisomer
phosphorus, sulphur and silicon forms a tetrahedral structure has betablocking activity while Disomer has no betablocking
with four different groups attached to them. They form two activity. The action potential prolonging potential is due to
nonsuperimposable mirror images. Most optical active drugs Lisomer; Nebivolol has highly selectively beta1blocking effects,
are chiral as a result of the presence of asymmetrically while the Lisomers causes vasodilatation; Most beta2selective
tetrahedral carbon atoms. The individual mirror image forms agonist drugs are formulated as a racemic mixture of Rand
of a chiral molecule are called optical isomers because they Sisomers. Only the Risomer has the beta2agonistic activity
rotate the plane of polarized light i.e., they are optically active while Sisomer has no beta2agonistic activity, even Sisomer
and differ in structure only in the orientation of atoms.Today, promotes the inflammation. Now a days, Salbutamol is available
optical isomers are more commonly referred as enantiomers as a single isomeric preparation of Risomer as levalbuterol;[5,9]
or an enantiomeric pair.[7,8] Ibuprofen is a racemic mixture; Sibuprofen is active form and
Ribuprofen is inactive. Dexibuprofen, its active enantiomer, is
Optical isomers or enantiomers have same physical and marketed now as single enantiomer with an effective dose of
chemical properties like identical melting points, pKa, 50% of ibuprofen and fewer side effects;[11] Halothane, enflurane,
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and isoflurane are chiral drugs with different anesthetic pharmacology. Currently a large number of clinical trials
potencies;[5,9] D (+) 2R,3S propoxyphene is analgesic while() are going on to compare the efficacy and safety of single
2S,3R propoxyphene has antitussive action.[12] enatiomers and the racemic mixture. Many single enantiomer
drugs will hopefully flood the market in near future.
Isomerism can lead to different therapeutic uses and
adverse drug reactions like Quinine has antimalarial activity References
while quinidine has an antiarrythmic property; Lsotalol is
1. McNaughtAD, WilkinsonA. IUPAC. Compendium of Chemical
alphablocker while dsotalol is antiarrythmic; Levomethorphan
Terminology. 2nded.(the Gold Book). Oxford: Blackwell Scientific
is a potent opiod analgesic while dextromethorphan is a cough Publications; 1997. XML online corrected version. Available from:
suppressant;[5,9] RThalidomide is sedative while SThalidomide http://goldbook.iupac.org/E02069.html(Last updated 2012Aug19,
has been shown teratogenic effects;[13] RNaproxen is used for Last accessed on 2012Nov30).
2. McNaughtAD, WilkinsonA. IUPAC. Compendium of Chemical
arthralgic pain while SNaproxen is teratogenic;[5] DEthambutol
Terminology. 2nded.(the Gold Book). Oxford: Blackwell Scientific
is antituberculosis drug while Lethambutol has been found to Publications; 1997. XML online corrected version. Available from:
cause blindness;[14] (S) (+)ketamine causes fewer psychotic http://goldbook.iupac.org/E02072.html(Last updated 2012Aug19,
emergence reactions, less agitated behavior, and better Last accessed on 2012Nov30).
3. Harpers illustrated biochemistry. In: MurrayR, BenderD, BothamKM,
intraoperative amnesia, and analgesia than its enantiomer;
KennellyPJ, RodwellV, WeilPA, editors. Harpers Illustrated
Ldopa, used in treatment for Parkinsons disease has an isomer Biochemistry. 29thed. NewYork: Lange Medical Books/McGrawHill
Ddopa which has never been used because it causes deficiency Medical Publishing Division; 2012.
of white blood cells and thus susceptibility to infections.[5,9] 4. RileyTN, DeRuiterJ, RavisWR, ClarkRC. Isomerism. In: SwarbrickJ,
editor. Encyclopedia of Pharmaceutical Technology. 3rded, 6thVol.
London: Informa Healthcare; 2006. Available from: http://www.
Two stereoisomers can compete for binding to same receptors studytemple.com/forum/pharmacology/899encyclopediapharmaceuti
like Smethadone antagonizes respiratory depression action of caltechnology-thirdedition6volumesetjamessw.html(Last accessed
Rmethadone. If the two isomers are of agonist and antagonist 2012March 31).
5. Basic and Clinical Pharmacology In: KatzungBG, MastersSB, TreverAJ,
type, then racemic mixture acts as partial agonist like picendol
editors. 11thed. Noida, UP, India: Tata MacgrawHill; 2009.
and sulfinpyrazone inhibits the metabolism of SWarfarin 6. McConathyJ, OwensMJ. Stereochemistry in Drug Action. Prim Care
significantly but not of RWarfarin.[5,9] Companion J Clin Psychiatry 2003;5:703.
7. DeRuiterJ. Isomerism and Stereochemistry. Principles of drug action
Single Enantiomers vs. Racemic I, Winter 2005;1:111.
Conclusions
How to cite this article: Chhabra N, Aseri ML, Padmanabhan D. A review of
Research in the field of stereoisomerism has opened the new drug isomerism and its significance. Int J App Basic Med Res 2013;3:16-8.
Source of Support: Nil. Conflict of Interest: None declared.
challenges and the new field avenues in the field of clinical
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