The Chemistry of Adderrall - Research Paper Example

Rebecca Russell Chem 130 The Chemistry of Adderrall Introduction Adderall is a “central nervous system stimulant Adderall Adderall affects chemicals in the central and autonomic nervous system that play a special role in “hyperactivity and impulse control” (“Adderall”). Adderral is actually “both a d-amphetamine and l-amphetamine” (Harrison), where the d-amphetamine acts mainly on “dopaminergic systems” while l-amphetamine is norepinephrinergic (Harrison). “Dopaminergic” refers to the involvement of Adderall in reward pathways while “norepinephrinergic” somehow refers to its role in sympathetic nervous response. Brief History of the Drug Adderall used to be called “Obetrol,” and was approved by the FDA in the 1960’s. nevertheless, its lack of popularity made Rexar Pharmaceuticals to sell its formula rights to Shire Richwood in 1994. Two years later, the FDA approved the new drug “Adderall” for the “treatment of ADHD in children” (Geist 4). However, in the years that followed, Adderall, which is prescribed in 5, 10, 15, 20, 25 or 30 mg doses, has caused multiple side effects among its users (Geist 4; “Information for Healthcare”), which makes it as of now a Schedule II drug, or a drug with accepted safe medical uses but with a high risk of abuse. Uses of Adderrall Adderall is mainly used in the treatment of narcolepsy and attention deficit hyperactivity disorder, or ADHD (“Adderall”). Other uses may include treatment of depression and weight loss (“Adderall Uses”). Metabolism of Adderrall in the Body A study conducted at St. Mary’s Hospital Medical School in London (Sever et al. 177) has shown that the urines of patients undergoing treatment with amphetamines, including Adderall, naturally leads to the excretion of urine containing the chemicals norephidrine and hydroxynorephidrine. Although the amount of the chemicals norephidrine and hydroxynorephidrine in the human tissues cannot exactly be determined based on the quantities of these two chemicals in the urine, it remains a fact that this amount is actually “five times as much” as what is normally produced (Sever et al. 177). These particular chemicals produced during the metabolism of Adderall in the body – norephidrine and hydroxynorephidrine – are believed to “increase the risk of stroke” (“L-Norephidrine antibody”). Norephidrine is also known as phenylpropanolamine, which is a drug component primarily used “to relieve allergic reactions or respiratory infections.” (“L-Norephidrine antibody”) Furthermore, one should know that it is in fact the metabolism of amphetamines or Adderall or any other drug that naturally produces its desired or undesirable effects. As for an amphetamine like Adderall, as soon as it is ingested, it oxidizes “at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or norpholedrine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine, or norephidrine” (“Adderall Official FDA”). To determine the formation of 4-hydroxyamphetamine or norpholedrine, one should first number the carbon atoms in the benzene ring in a clockwise manner from the point where the propane chain is attached, then number 4 carbon is on the lower left hand corner of the ring. This “oxidizes” or combines with oxygen to form a hydroxyl or OH group. The resulting chemical, 4-hydroxyamphetamine, is now the same molecule of amphetamine but with an OH group attached to the lower left hand corner of the benzene ring. It can be illustrated as follows: The resulting chemical, 4-hydroxyamphetamine, is believed to cause side effects such as “severe allergic reactions,” “difficulty breathing,” “behavioral changes,” “shortness of breath,” “vomiting,” and many others. (“Hydroxyamphetamine/Tropicamide”) The other chemical that can possibly result from the metabolism of amphetamine in the body is beta- or alpha-hydroxyamphetamine, or norephidrine. This is formed when the oxidation happens at the side chain α or β carbon. Based on Organic Chem 130 lessons, the α is the first carbon that attaches to the functional group and this is followed by the β carbon. Therefore, in the structure of the amphetamine, oxidation of the α or β carbon will result in the formation of a hydroxyl group at either the CH point adjacent to NH2 or the CH2 point adjacent to CH. The following structure is a beta-hydroxyamphetamine, or norephidrine: Norephidrine is, as previously mentioned in the study of Sever and his colleagues, involved in increasing the risk of stroke. (“L-Norephidrine antibody”) The above diagrams and processes refer to the oxidation of the general amphetamine molecule. The chemical components of Adderall, on the other hand, are made up of two molecules of amphetamine with other functional groups, therefore the oxidation may happen at either of the two amphetamine molecules. Controversies Adderall did not enjoy much popularity in the past and even now because the US FDA’s Adverse Event Reporting System database reveals 12 identified cases of sudden death among users of Adderall or Adderrall XR who are from 1 to 18 years of age from 1999 to 2003 (“Information for Healthcare”). An in-depth look into the 12 sudden death cases revealed that the risk factors involved “undiagnosed cardiac abnormalities [such as] aberrant origin of coronary artery” (“Information for Healthcare”). Other risk factors included “[another] illness and very rigorous exercise” (“Information for Healthcare”), although the fact remains that further investigation is necessary to establish a definite cause for deaths caused by Adderall. Aside from the records of death cases due to Adderall, the side effects of the drug similarly post a threat to patients and potential users. Based on official FDA information on Drugs.com, Adderall produces side effects such as an increase in the symptoms of “behavior disturbance and thought disorder,” “suppression of growth” among children, “increases in blood pressure,” worsening of “motor and phonic tics [as well as] Tourette’s syndrome,” “decreased appetite,” and several interactions with various drugs (“Adderall Official FDA”). All these known side effects, coupled with actual records of deaths, leave several potential users of Adderall wondering whether taking such a drug is definitely worth it or not at all. Chemical Structure and Formula Adderrall is a drug which is a combination of equal amounts of four amphetamine salts namely “dextroamphetamine Saccharate, dextroamphetamine Sulfate, di-amphetamine Aspartate, and di-amphetamine Sulfate” (“Chemistry of Adderrall,” Drugs Forum.com). These four amphetamine salts are basically amphetamines with functional groups. Basically, the amphetamine molecule has the chemical name 1-phenylpropan-2-amine. This means that the amphetamine is basically a propane with a basic chemical formula of CH3-CH2-CH3. The phenyl group, which is a functional group characterized by a benzene ring of alternating double and single bonds, is attached to the first carbon of the propane. Moreover, the amino group is attached to the second carbon, resulting in the crude chemical name of 1-phenyl, 2-amino propane. However, since the amino group is the active functional group in this new molecule which was basically propane, the name changes to 1-phenylpropan-2-amine. This translates as an amine, with a basic formula R-NH2, where R represents a phenyl group and a propane chain. The “1” means the first carbon, where the phenyl group is attached, while the “2” indicates the second carbon, where the amino group is attached. The structure is then illustrated as follows: If this structure were simplified to show the double bonds in the phenyl group as well as only the methyl and amino groups, the structure would then appear as: The amphetamine molecule therefore has a basic structure of C9H13N if all the carbon, hydrogen and nitrogen atoms are counted in the molecule. Now, one of the four amphetamine salts that make up Adderall is known as dextroamphetamine Saccharate, with a chemical formula of (C9H13N)2.C6H10O8 and with a molecular weight of 480.56, has the chemical name (+)-α-Methylphenylamine saccharate. (“Chemistry Reviews,” US Food and Drug Administration) The second amphetamine salt in Adderral is dextroamphetamine Sulfate, with a chemical formula (C9H13N)2.H2SO4 and with a molecular weight of 368.50. This particular amphetamine salt has the chemical name (+)-α-Methylphenylamine sulfate (“Chemistry Reviews,” US FDA). The same process is followed as above when this salt is formed, only that the NH3+ end of the amphetamine chemically combines with the SO4- ion of the sulfate group. The third amphetamine salt contained in Adderral is called di-amphetamine Aspartate, which is written as (C9H13N)2.C4H7NO4.H2O and which has a molecular weight of 286.33. This salt is known by its chemical name (±)-α-Methylphenylamine aspartate. (“Chemistry Reviews,” US FDA) The last active component of Adderrall is an amphetamine salt known as di-amphetamine Sulfate, with a chemical formula (C9H13N)2.H2SO4 and with a molecular weight of 368.50. this salt has the chemical name (±)-α-Methylphenylamine sulfate. (“Chemistry Reviews,” US FDA). The four salts that make up Adderall all combine to trigger a host of chemical reactions that give the drug its beneficial effects as well as its side effects. However, the mechanism of these effects can only be explained by pharmacology. Conclusion Adderall is a drug which is just like any other drug that has benefits and side effects. The question of whether to take Adderall or not usually lies in whether the benefits outweigh the risks. Currently, Adderall is a Schedule II drug as declared by the FDA. Therefore, only further research will be able to determine its fate as a pharmaceutical product. Moreover, I would like to say that the knowledge of the functional groups and chemical formulas which I got from Organic Chem 130 made me understand the chemical structure of Adderall and amphetamines in general. Now, I have learned that the harm caused by amphetamines is due to the oxidation of either the number 4 carbon of the benzene ring, or the α or β carbon of the propane chain. This seemingly simple chemical reaction will form two other chemicals that can cause the side effects. Although it is only pharmacology that can explain how these chemicals affect the body, somehow the things I have learned from Chem 130 explained to me what may happen in the molecular level when medicine is taken in. Top of Form Bottom of Form Works Cited “Adderall Official FDA Information.” ADHD. Drugs.com, 2010. Web. 1 Dec 2010. “Adderall Uses.” eMedTV: Health Information Brought to Life. Clinaro Inc., 2010. Web. 29 Nov 2010. “Adderall.” ADHD. Drugs.com, 2010. Web. 1 Dec 2010. “Chemistry of Adderall.” Adderall. Drugs-Forum.com, 2010. Web. 29 Nov 2010. “Chemistry Reviews.” Center for Drug Evaluation and Research. U.S. Food and Drug Administration, 2010. Web. 1 Dec 2010. Geist, Jared. “Focusing in on Adderall.’” Institute for Food Laws and Regulations. Michigan State University, 7 Dec 2007. Web. 2 Dec 2010. Harrison, Karl. “Adderall @ 3Dchem.com.” Macromolecules. 3Dchem.com, 2008. Web. 30 Nov 2010. “Hydroxyamphetamine/Tropicamide Side Effects.” Drugs Beginning with Hy. Drugs.com, 2010. Web. 1 Dec 2010. “Information for Health Care Professionals: Adderall and Adderall XR (amphetamine).” Postmarket Drug Safety Information for Patients and Providers. U.S. Food and Drug Administration, 2010. Web. 3 Dec 2010. “L-Norephidrine antibody (ab53190).” Drugs and Chemicals. Abcam.com, 2010. Web. 3 Dec 2010. < http://www.abcam.com/L-Norephedrine-antibody-ab53190.html> Sever PS, Caldwell L, Dring LG and Williams RT. “The Metabolism of Amphetamine in Dependent Subjects.” SpringerLink: European Journal of Clinical Pharmacology 6.3 (1973): 177-180. Web. 2 Dec 2010. Read More