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The Chemical Groups of Antipsychotics

Approximately ten percent of the world’s people suffer from psychosis. These people may be affected by schizophrenia or a schizophrenic-like disorder, a delirious condition, brief psychotic disorders, mania, an affective disorder with psychotic symptomatology, or a psychotic disorder from somatic disease. Antipsychotics, or neuroleptics, are needed to allow these people live normal lives.

These drugs do not completely cure people of psychosis, but they are very effective in treating the terrible symptoms. They sedate, calm, and improve the behavior of patients, allowing them to behave normally. Typical antipsychotics, the older medications, have many side effects. In order to reduce some of the side effects, atypical antipsychotics were developed in the 1990’s. The most recent type of antipsychotics, partial dopamine agonists, is now in the process of being developed.

Chemically, neuroleptics can be divided into six groups: phenothiazines, thioxanthenes, butyrophenones, dihydroindolones, dibenzoxazepines and dibenzdiazepines, diphenylbutylpiperidines, and others like sulpiride and lithium drugs. These drugs have varying structures and work in different ways.

Phenothiazines are mainly composed of a tricyclic system, the central ring of which contains a nitrogen atom and a sulfur atom. This is a picture of the molecular structure of Fluphenazine, a phenothiazine derivative:

The core structure of thioxanthene derivatives is the same as that of phenothiazines except the nitrogen atom is replaced by a carbon atom that is attached to a side chain. Thioxanthenes work the same way as phenothiazines and produce the same effects. Both types of drugs work by binding to the dopamine receptors, D1 and D2. This is a picture of how one thioxanthene derivative, chlorprothixene, is synthesized:

All butyrophenone derivatives are of the piperidine and piperazine series and have a pfluorobutyrophenone group. They act much like phenothiazines and thioxanthenes but mostly just bind to D2 receptors. The synthesis of a particular butyrophenone derivative, trifluperidol, is depicted here:

Diphenylbutylpiperidine derivatives are strong and long lasting. Their mechanism of action is mostly unknown, but they do slow dopaminergic activity. Penfluridol is synthesized through a Grignard reaction, alkaline hydrolysis, and alkylation:

Almost all antipsychotics work by blocking dopamine receptors (D1, D2, or D3 receptors) in the mesolimbic system of the brain. Phenothiazines block both D1 and D2 receptors whereas butyrophenones only bind to D2 receptors. Clozapine, a dibenzodiazepine derivative, is a poor blocker of dopamine receptors. It does reduce dopaminergic activity without blockage and antagonize 5-HT2A and 5-HT2C, to lessen negative symptoms.

The chemical groups of antipsychotics are all quite different structurally and have different mechanisms of action. Most of the drugs slow dopaminergic activity and they all sedate, calm, and reduce the psychosis of patients. They perform a great service to many people suffering from schizofrenia and other disorders.

By Mariel Hohmann

Quillivant XR Post Coming Up!

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More about Ritalin and Adderall

In our previous post, you learned that Ritalin and Adderall  are ADHD drugs that are often abused in order to improve focus while studying as seen here:

So how do these drugs work? What’s the difference? Why do they improve someone’s attention and what effects can they have?

About Ritalin

Ritalin, also known as methylphenidate, is the most common medication used to treat ADHD. It is a stimulant and in combination with therapy can significantly positively affect about 70-80% of those with ADHD who take it. Ritalin works to make it possible for a person to behave more normally, but the person must still learn what normal behavior is. In the biochemical sense, Ritalin inhibits the dopamine transporter of the brain preventing it from removing dopamine from the space outside of the cells. This allows the dopamine to activate more receptors. As dopamine is associated with focus and motivation, this helps treat ADHD symptoms. Therefore, Ritalin helps someone be focused on something longer than possible otherwise. This is what makes the drug appeal to many students. They find it helps them focus more, so they can successfully complete more work than they normally would.

However, Ritalin, as all medications do, comes with side effects. In fact, Ritalin’s side effects is enough to stop 10% of adults and 5% of adolescents to stop taking the medication. The side effects of Ritalin include:

  • Dry mouth
  • Decreased appetite
  • Moodiness/mood changes (including increased anxiety or sadness)
  • Decreased weight
  • Nausea and dizziness
  • Palpitations
  • Tachycardia chest pain
  • Motor or verbal tics
  • Hallucinating
  • Believing things that are not true

More importantly, Ritalin is an addictive drug. Meaning, the students that take it just for one test may slowly find themselves needing more and more to function. Long term usage can lead to both stunted growth and  cardiovascular problems. It can even cause psychotic and delusional episodes and increased aggression.

About Adderall

Adderall is a very similar drug to Ritalin that consists of a mix of amphetamine salts. It is also used to treat ADHD.  Adderall also  inhibits the dopamine transporter of the brain preventing it from removing dopamine from the space outside of the cells. However, it goes even further by going inside the cells and making them pump out dopamine.  In this way, Adderall is slightly stronger of a medication. Adderall is just about as effective as Ritalin, but studies have shown some slight advantage of Adderall over Ritalin. There is no significant difference. Adderall, like Ritalin, is abused my many students to increase their studying abilities.

Adderall also comes with its fair share of side effects including:

  • Nervousness
  • Restlessness
  • Vomiting
  • Constipation
  • Weight loss
  • Uncontrollable shaking
  • Stomach pain
  • Trouble falling asleep or staying asleep
  • Seizures
  • Slow or difficult speech

Normally before taking Adderall, a person’s cardiovascular or neurological problems must be assessed to prevent further problems. Unprescribed Adderall can have serious consequences.

“There’s death—that’s the worst case, but there are people who end up with strokes, people who have seizures, all kinds of medical complications.”  Dr. Joe Frascella of the National Institute on Drug Abuse

Adderall can have serious effects to someone’s heart, and like Ritalin, Adderall is very addictive. It can even be a gateway drug to serious drugs like cocaine and heroine.

With both drugs, it is clear that unprescribed use is a serious problem and cannot continue. Students are putting themselves in danger just for a higher grade in class and that surely can’t be worth the A.

Author: Maggie Martinez

The Rampant Misuse of ADHD Pills

Adderall is another ADHD drug used to increase studying ability.

Check out a news report on it here.

More on Ritalin, Adderall and the chemistry behind them to come!

 

Author: Maggie Martinez

Topical Teaching

 

A few years ago stories like this one were rare. Now few years down the track,  the misuse of medication among students has become a huge concern:

HSC students are taking illegally obtained prescription medication used to treat ADHD to help cram for their final school exams, which start tomorrow.

The Sun-Herald spoke to students from five schools across Sydney last week who admitted to using the medication, saying it improved their focus during study.

But medical experts warn that they are risking side effects as serious as psychosis and heart problems.

As students try to maximise their study hours, some are exchanging tips on internet forums about the most effective methods of combating fatigue. Comments posted on the boredofstudies.org website include debates about the effectiveness of caffeine pills and prescription medication, as well as cocaine and the hallucinogenic drug DMT.

A year 12 student from Ryde Secondary College…

View original post 177 more words

Research on Alternative Treatment Options for ADHD

There has been a recent increase of the use of atypical antipsychotics as a treatment option for ADHD. An article published in September 2012 recently looked at a number of these atypical treatments to evaluate the effectiveness and safety of these methods. The drugs were compared to a placebo in the experiment. The test subjects consisted of youth and children 18 years of age and younger that have previously been diagnosed with ADHD.   8 trials were performed in total between the years of 2000 and 2008.

Caution in drawing a definite conclusion is required for the following reasons:

  1. Some of the studies produced inadequate, non-conclusive results.
  2. The evidence is affected by the heterogeneous population used for the studies. Other factors may have contributed to the results.
  3. There were methodological issues in some studies, such as use of enriched designs and risk of selection bias.
  4. No study addressed the issue of pre-existing/concurrent psychosocial interventions, and comorbid stimulant medication and its dosage was only partially addressed.
  5. No child under 5 was tested on

A majority of the trials revolved around a drug known as risperidone. It is usually found in the form of a tablet.  Risperidone is traditionally used in the cases of schizophrenia or episodes of mania due to bipolar disorder. The drug changes the activity of certain natural substances found in the brain.

Risperidone has a structure of 2-methyl-3-vinyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one as can be seen in this stick structure. Each line is a bond and if an element is not labeled, it assumed to be carbon. It is also assumed that the appropriate number of hydrogen to fulfill the octet rule is attached to these carbons.

There was some limited evidence that ripseridone has a short-term effect in reducing the aggression of ADHD children. On the ABC irritability subscale (ranging from 0-49), there was a difference in scores of 6.49 points. This may be clinically significant. On the Nisonger Child Behaviour Rating Form – Conduct Problem subscale (ranging from 0-48), there was an 8.61 point score difference. One study suggests that these results last to some extent for up to 6 months.

Quetiapine furmate was also tested in this study. This drug, like ripseridone, is a psychoactive organic compound most commonly used to treat  schizophrenia. It is also commonly found in oral pill form.

Quetiapine-furmate, or 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol hemifumarate, has a molecular formula of 2(C21H25N3O2S).C4H4O4. .  This image also shows a stick figure representation of the drug. The same rules apply to this structure

No significant evidence was found suggesting that quetiapine furmate works effectively to treat disruptive behavioral disorders in children.

Further research needs to be done on the topic to confirm or deny the effectiveness of anti-psychotic drugs as an alternative treatment for ADHD. Although it is being currently prescribed, success may only be a result of placebo. It seems that risperidone, however, does have an actual significant effect to treat ADHD.

Author: Maggie Martinez