Enantiopure drug
Encyclopedia
An enantiopure drug is a pharmaceutical that is available in one specific enantiomer
ic form. Most biological molecules (proteins, sugars, etc.) are present in only one of many chiral
forms, so different enantiomers of a chiral drug molecule bind differently (or not at all) to target receptor
s. One enantiomer of a drug may have a desired beneficial effect while the other may cause serious and undesired side effects, or sometimes even beneficial but entirely different effects.
Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers, either by specifically manufacturing the desired enantiomer or by resolving a racemic
mixture. On a case-by-case basis, the U.S. Food and Drug Administration (FDA) has allowed single enantiomers of certain drugs to be marketed under a different name than the racemic mixture. Also case-by-case, the United States Patent Office has granted patents for single enantiomers of certain drugs. The regulatory review for marketing approval (safety and efficacy) and for patenting (proprietary rights) is independent, and differs country by country.
and single-enantiomer
form.
The following are cases where the individual enantiomers have markedly different effects:
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
ic form. Most biological molecules (proteins, sugars, etc.) are present in only one of many chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
forms, so different enantiomers of a chiral drug molecule bind differently (or not at all) to target receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s. One enantiomer of a drug may have a desired beneficial effect while the other may cause serious and undesired side effects, or sometimes even beneficial but entirely different effects.
Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers, either by specifically manufacturing the desired enantiomer or by resolving a racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
mixture. On a case-by-case basis, the U.S. Food and Drug Administration (FDA) has allowed single enantiomers of certain drugs to be marketed under a different name than the racemic mixture. Also case-by-case, the United States Patent Office has granted patents for single enantiomers of certain drugs. The regulatory review for marketing approval (safety and efficacy) and for patenting (proprietary rights) is independent, and differs country by country.
Examples
The following table lists pharmaceuticals that have been available in both racemicRacemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
and single-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
form.
| Racemic mixture | Single-enantiomer |
|---|---|
| Amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,... (Benzedrine Benzedrine Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928... ) |
dextroamphetamine Dextroamphetamine Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite.... (Dexedrine) |
| Bupivacaine Bupivacaine Bupivacaine is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.-Indications:... (Marcain) |
levobupivacaine Levobupivacaine Levobupivacaine is a local anaesthetic drug belonging to the amino amide group. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by Abbott under the trade name Chirocaine.-Clinical use:... (Chirocaine) |
| Cetirizine Cetirizine Cetirizine , a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria.-Availability:... (Zyrtec / Reactine) |
levocetirizine Levocetirizine Levocetirizine is a third-generation non-sedative antihistamine, developed from the second-generation antihistamine cetirizine. Chemically, levocetirizine is the active enantiomer of cetirizine. It is the L-enantiomer of the cetirizine racemate. Levocetirizine works by blocking histamine receptors... (Xyzal) |
| Citalopram Citalopram Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S... (Celexa / Cipramil) |
escitalopram Escitalopram Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S... (Lexapro / Cipralex) |
| Methylphenidate Methylphenidate Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity... (Ritalin) |
dexmethylphenidate Dexmethylphenidate Dexmethylphenidate, otherwise known as d-threo-methylphenidate , is the dextrorotatory enantiomer of methylphenidate. It is a norepinephrine-dopamine reuptake inhibitor and releasing agent and thus a psychostimulant, which affects the CNS... (Focalin) |
| Modafinil Modafinil Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea... (Provigil) |
armodafinil Armodafinil Armodafinil is a stimulant-like drug produced by the pharmaceutical company Cephalon Inc., which was approved by the FDA on June 15, 2007... (Nuvigil) |
| Ofloxacin Ofloxacin Ofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class considered to be a second-generation fluoroquinolone. The original brand, Floxin, has been discontinued by the manufacturer in the United States on 18 June 2009, though generic equivalents continue to be... (Floxin) |
levofloxacin Levofloxacin Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class and is used to treat severe or life-threatening bacterial infections or bacterial infections that have failed to respond to other antibiotic classes. It is sold under various brand names, such as Levaquin and... (Levaquin) |
| Omeprazole Omeprazole Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome... (Prilosec) |
esomeprazole Esomeprazole Esomeprazole is a proton pump inhibitor developed and marketed by AstraZeneca which is used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease and Zollinger-Ellison syndrome... (Nexium) |
| Salbutamol Salbutamol Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names.... (Ventolin) |
levalbuterol Levalbuterol Levosalbutamol or levalbuterol , trade name Xopenex, is the R-enantiomer of the short-acting β2-adrenergic receptor agonist salbutamol. It is marketed by Cipla as Levolin, & by axa named Axazest.-Uses:... (Xopenex) |
| Zopiclone Zopiclone Zopiclone is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the name Lunesta... (Imovane) |
eszopiclone Eszopiclone Eszopiclone, marketed by Sepracor under the brand-name Lunesta, is a nonbenzodiazepine hypnotic used as a treatment for insomnia. Eszopiclone is the active dextrorotatory stereoisomer of zopiclone, and belongs to the class of drugs known as cyclopyrrolones.Eszopiclone is a short acting... (Lunesta) |
The following are cases where the individual enantiomers have markedly different effects:
- ThalidomideThalidomideThalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
: Thalidomide is racemic. One enantiomer is effective against morning sicknessMorning sicknessMorning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
, whereas the other is teratogenic. However, the enantiomers are converted into each other in vivoIn vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
,. Dosing with a single-enantiomer form of the drug will still lead to both the D and L isomers eventually being present in the patient's serum and thus would not prevent adverse effects (though it might reduce them if the rate of in vivo conversion can be slowed). - EthambutolEthambutolEthambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
: Whereas one enantiomer is used to treat tuberculosisTuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, the other causes blindness. - NaproxenNaproxenNaproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
: One enantiomer is used to treat arthritis pain, but the other causes liver poisoning with no analgesic effect. - SteroidSteroidA steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
receptor sites also show stereoisomerStereoisomerismStereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but that differ only in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections...
specificity. - PenicillinPenicillinPenicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
's activity is stereodependent. The antibiotic must mimic the D-alanine chains that occur in the cell walls of bacteria in order to react with and subsequently inhibit bacterial transpeptidase enzyme. - Only L-propranolol is a powerful adrenoceptor antagonist, whereas D-propranolol is not. However, both have local anestheticLocal anestheticA local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
effect. - The L-isomer of Methorphan, levomethorphanLevomethorphanLevomethorphan is the l-stereoisomer of methorphan. The effects of the two isomers are quite different. Dextromethorphan is an antitussive at low doses and a dissociative at much higher doses, whereas levomethorphan is an opioid analgesic...
is a potent opioid analgesic, while the D-isomer, dextromethorphanDextromethorphanDextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
is a dissociative cough suppressant. - (S)-(–) isomer of carvedilolCarvedilolCarvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...
, a drug that interacts with adrenoceptors, is 100 times more potent as beta receptor blockerBeta blockerBeta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
than (R)-(+) isomer. However, both the isomers are approximately equipotent as alpha receptor blockers. - The D-isomers of amphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
and methamphetamineMethamphetamineMethamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
are strong CNS stimulants, while the L-isomers of both drugs lack appreciable CNS(central nervous system) stimulant effects, but instead stimulate the peripheral nervous system. For this reason, the Levo-isomer of methamphetamine is available as an OTC nasal inhaler in some countries, while the Dextro-isomer is banned from medical use in all but a few countries in the world, and highly regulated in those countries who do allow it to be used medically. - KetamineKetamineKetamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
is commonly composed of R & S enantiomers that have different dissociative and hallucinogenic properties, whereas the S enantiomer EsketamineEsketamineEsketamine or -ketamine is a general anaesthetic of the dissociative class by way of the central nervous system and has its mode of action as an NMDA receptor antagonist...
is more potent in isolation as a dissociative.