Stimulants pemoline

One benefit of pemoline s milder effects is that it appears to have less abuse potential than the other stimulants. Pemoline is a schedule IV drug, in contrast to other stimulants that are schedule II. The side effects of pemoline are similar to other stimulants but in a milder form. The most common side effects are loss of appetite, nausea, and insomnia. Rarer side effects include headache, dizziness, changes in mood, increases in blood pressure or pulse, and psychosis. 

PemoUne is an oxazolidinone derivative that is not structurally similar to amphetamine or methylphenidate. It has fewer stimulating properties than other stimulants and may have less abuse potential. Unlike most other stimulants, pemoline is a Schedule IV agent and does not require a triplicate prescription. However, there are numerous reports of hepatotoxicity in patients taking pemoline (see review by Safer et al. 2001), and it is no longer available in the United States. 

In 1995, CHADD also had smaller grants from Abbott Laboratories ( 37,000) and Burroughs Wellcome ( 18,000). Abbott is the manufacturer of the stimulant pemoline (Cylert), used to treat ADHD. Burroughs Wellcome makes several medications used in pediatric medicine, including well-known antibiotics and cold medications. They also make the highly stimulating antidepressant Wellbutrin. 

Although pharmacologic activity similar to other CNS stimulants, pemoline has minimal sympathomimetic effects... 

Pemoline [2152-34-3] (24), stmcturally dissimilar to amphetamine or methylphenidate, appears to share the CNS-stimulating properties. As a consequence, pemoline is employed in the treatment of ADHD and of narcolepsy. There are several other compounds that are stmcturally related to amphetamines, although not as potent and, presumably, without as much abuse potential. These compounds also have anorexic effects and are used to treat obesity. Some of the compounds available are phentermine [122-09-8] fenfluramine [458-24-2] and an agent that is available over-the-counter, phenylpropanolamine [1483815-4] (26). 

Pemoline (Cylert). Pemoline was introduced as an alternative stimulant. Its two key advantages are that it can be taken once a day, though with the extended-release versions of methylphenidate and Adderall this is less of an issue, and it may be less prone to abuse. It was generally believed that pemoline has a gradual onset of action, taking several weeks to reach full therapeutic benefit, but some researchers discount this assumption. 

Pemoline is less potent than the other available stimulants. It is started at 18.75 mg each morning and is increased in increments of 18.75 mg every week or two. The maximum dose is 112.5mg/day, though some patients do require higher doses. Because pemoline is less potent than other stimulants, it is more likely to be ineffective even at its higher doses. When pemoline does not relieve the symptoms of ADHD, patients should be changed to a different stimulant. 

One benefit of pemoline s milder effects and slower onset of action is that it appears to possess less abuse potential than other stimulants. The abuse potential, however, is usually a concern not for patients who are prescribed the stimulant, but for others who may want to buy it on the street or steal the pills from someone else. Although pemoline does have some potential for abuse, it is limited. 

Close to 70% of children with ADHD will respond to a stimulant. When the child is not helped by the first stimulant that is prescribed, there is still a good chance of responding to a different one. If an initial trial of methylphenidate isn t successful, then switching to dextroamphetamine or Adderall is a reasonable strategy. If dextroamphetamine or Adderall was used first and did not work well, then we recommend switching to methylphenidate. Because dextroamphetamine and Adderall are more similar, it makes less sense to switch between these two. We do not recommend pemoline as a first-line treatment. 

Monoamine oxidase inhibitors Paroxetine Protriptyline Sertraline Venlafaxine Stimulants Atomoxetine Dextroamphetamine Methylphenidate Modaflnil Pemoline... 

CNS stimulants can be classified as Psychomotor stimulants compounds that display a stimulatory effect primarily on brain functions and which activate mental and physical activity of the organism. They are made up of methylxanthines (caffeine, theophylline, pentoxifyllin), amphetamines (dextroamphetamine, methamphetamine), and also methylphenidate and pemoline. Respiratory stimulants or analeptics compounds, which cause certain activations of mental and physical activity of the organism, and primarily excite the vasomotor and respiratory centers of the medulla (doxapram, almitrine).Drwgi that suppress appetite or anorectics drags that activate mental and physical activity of the organism, but primarily accentuate the excitatory center of satiation in the hypothalamus (phentermine, diethylpropion).In order to increase mental capability, nootropics — drugs that increase the functional state of the brain — are sometimes used, the effect of which is associated with blood flow and metabolism of the brain. 

Pemoline is a structurally unique CNS stimulant that exhibits minimal sympatomimetic effects, and possesses the same pharmacological properties as amphetamines and methylphenidate, yet it has less potential to cause addiction than other CNS stimulators. It enhances vigilance and motor activity, and causes weak euphoria, which is possibly linked to an increase in dopaminergic transmissions in CNS structures. 

The therapeutic indications for the psychomotor stimulants are quite limited. They are beneficial in the treatment of the hyperkinetic syndrome (attention deficit-hyperactivity disorder with minimal brain dysfunction). This is generally a childhood disease characterized by hyperactivity, inability to concentrate, and impulsive behavior. Amphetamines and the more extensively used methylphenidate paradoxically are quite effective in calming a large proportion of children with this disorder. Pemoline Cylert) is also used in the treatment of attention deficit disorder with hyperkinetic behavior. The mechanism by which these compounds are effective in this disorder is not known. 

The synthesis of 2-amino-4(5//)-oxazolones has been a very productive area of research since Traube and Ascher first prepared 2 nearly 90 years ago. Subsequently, literally hundreds of analogues have been prepared and evaluated, primarily as medicinal agents. For example, pemoline (Cylert ) 68 (Fig. 6.9), a central nervous system (CNS) stimulant relatively devoid of side affects has been... 

Stimulant treatment of ADHD has generated the largest body of treatment literature of any childhood psychiatric disorder. Between 1962 and 1993, over 250 reviews and over 3000 articles were published on stimulant effects (Swanson, 1993). By 1996, 161 randomized controlled trials (RCTs) had been published, encompassing 5 preschool, 150 school-age, 7 adolescent, and 9 adult studies. Improvement occurred in 65 %-75% of the children randomized to stimulants (meth-ylphenidate) [MPH] n = 133 trials dextroamphetamine [DEX] n = 22 trials pemoline [PEM] n = 6 trials) compared to 5%-30% of those assigned to pla-... 

Although side effects of other stimulants respond to dose reduction or change in time of administration, PEM use can be associated with serious, irreversible liver damage. Postmarketing surveillance revealed abnormalities in liver function tests in 44 children receiving PEM acutely or chronically (Berkovitch et ah, 1995). Even more disturbing, 13 children on PEM experienced total liver failure—11 resulting in death or transplant within 4 weeks of failure. This exceeds the rate in the normal population by 4 to 17 times. Pemoline, therefore, is reserved for alternative treatment only if the patient fails to tolerate all three stimulants (MPH, DEX, and AMP) and subsequent trials of an-... 

Page, J.G., Bernstein, J.E., Janicki, R.S., and Michelli, F.A. (1974) A multicenter trial of pemoline (cylert) in childhood hyperkinesis. In Conners, C.K., ed. Clinical Use of Stimulant Drugs in Children. The Hague, Netherlands Excerpta Medica, pp. 98-124. 

Pelham, W., Greenslade, K., Vodde-Hamilton, M., Murphy, D., Greenstein, J., Gnagy, E., Guthrie, K., Hoover, M., and Dahl, R. (1990) Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline. Pediatrics 86 226-237. 

Another major safety concern in the treatment of youth with SUD is abuse of prescribed medications. Particular controversy has arisen around the use of stimulant medication in youth with SUD and ADHD. In one controlled study of adults, the use of methyl-phenidate (Ritalin) did not increase cocaine use or craving for cocaine (Grabowski et ah, 1997), suggesting that the abuse potential of stimulants may be overestimated. Riggs et al. (1996) did not report any difficulties with abuse when administering pemoline (Cylert) to a group of adolescents with SUD and ADHD. While Riggs and associates have observed that... 

A frequently used test to assess the effect of psychostimulants is the CPT. Methylphenidate at doses of around 0.3mg/kg usually improves performance, Le. reduces the number of errors, on the CPT whereas the effects of d-amphetamine (at doses between 5 and 20 mg) and pemoline (10 60mg) appear to be less reliable (Riccio et al., 2001). The stimulating effect of caffeine in various areas of performance is of shorter duration than that of... 

Cocaine, amphetamine, dextroamphetamine, methylphenidate, and pemoline are classified as psychomotor stimulants, producing an acute euphoria in control subjects, as well as a wide variety of responses in psychiatric patients. These stimulants are also effective in postponing the deterioration in psychomotor performance that often accompanies extreme fatigue, a property that may be useful in some carefully selected cases. 

This group of medications has been studied for the treatment of hyperactivity or ADHD since 1936 and has consistentiy shown robust efficacy in more than 150 randomized ciinicai triais (RCTs) of schooi-aged chiidren. There are more than 3,000 citations and 250 reviews of stimulant treatment (63, 64 and 65). Robust short-term stimulant-related improvement in ADHD has been reported in 161 controlled RCTs, including five preschool, 140 school-age, seven adolescent, and nine adult studies (66). There were 133 trials with methylphenidate, 22 with dextroamphetamines, and six with pemoline. In addition, two studies found treatment with mixed amphetamine salts to be superior to placebo (67, 68). 

Injection of botulinum toxin A at the site of problematic tics is sometimes helpful. Treatment of any associated attention deficit disorder (eg, with clonidine patch, guanfacine, pemoline, methylphenidate, or dextroamphetamine) or obsessive-compulsive disorder (selective serotonin reuptake inhibitors or clomipramine) may be required. Bilateral thalamic stimulation is sometimes worthwhile in otherwise intractable cases. 

The most commonly used agents to enhance attention in attention deficit disorder are the stimulants methylphenidate and ( -amphetamine. Other effective stimulants are not as widely used, pemoline because of liver toxicity and methamphetamine because of its greater abuse potential. Methylphenidate and ( -amphetamine act predominantly by releasing dopamine from presynaptic dopamine terminals (Figs. 12— 2 and 12—3). These agents not only block the dopamine transporter but may actually... 

In this chapter, we have looked at two topics in cognitive enhancement attention and memory. We have first reviewed the role of dopamine and norepinephrine/ noradrenaline in the neuropharmacology of attention, and then the syndrome of attention deficit disorder as a common problem associated with a disorder of attention. We then discussed the use of stimulants for improving attention, primarily in attention deficit disorder, and reviewed the pharmacological mechanisms of action of methylphenidate, d and 1 amphetamine, pemoline, and secondary therapies such as clonidine and guanfacine. 

The primary drug therapies are psychostimulants which are indicated for both emotional based sleep disorders (i.e., narcolepsy) as well as ADHD. The drugs of choice are Ritalin (methylphenidate), dextroamphetamine or Cylert (pemoline), all CNS stimulants that effect the monoamine systems. The current therapies provide symptomatic relief but the current medications are not without side effects, including abuse potential, cardiovascular effects, insomnia, appetite suppression, head and stomach aches, crying and nervous mannerisms. 

Pemoline, an oxizolidine compound, acts similarly to methylphenidate—through catecholamine uptake inhibition in the CNS (27) with minimal sympathomimetic effects (57). Although pemoline is not the first-line stimulant for the treatment of ADHD, it has been successfully used for the treatment of this disorder in both children and adults (28,30). Pemoline has also been used for the treatment of daytime sleepiness associated with narcolepsy (31), and although it is somewhat effective for this purpose (33), it is not a first-line choice owing to its potentially lethal liver toxicity. 

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