Methylphenidate effects

Bergman, A., Winters, L., and Cornblatt, B. (1991). Methylphenidate effects on sustained attention. In Greenhill, L. and Osman, B., eds. Ritalin Theory and Patient Management. New York Mary Ann Liebert, Inc., pp. 223-231. 

Murphy, D., Pelham, W., and Lang, A. (1992) Aggression in boys with attention deficit-hyperactivity disorder Methylphenidate effects on naturalistically observed aggression, response to provocation, and social information processing. J Abnorm Child Psychol 20 451-466. 

Pelham WE, Sturges J, Hoza J, et al Sustained release and standard methylphenidate effects on cognitive and social behavior in children with ADHD. Pediatrics 80 491-501, 1987... 

The authors have encountered some patients refractory to all other therapies who had a dramatic, full, rapid, and sustained response to methylphenidate. One study found methylphenidate effective in treating mildly depressed outpatients, particularly those who drank three or more cups of coffee a day ( 191). A replication study did not find a drug-placebo difference on the physician s ratings, but did demonstrate one for the patients subjective assessment of improvement ( 192). Another blind study of methylphenidate found improvement in an outpatient group (193). Finally, two of three trials of methylphenidate in apathetic, senile geriatric patients showed that this drug produced more improvement than placebo (194). To date, no evidence indicates that it is beneficial in cases of moderate-to-severe depression. 

Klein, R., Mannuzza, S. (1988b). Hyperactive boys almost grown up III. Methylphenidate effects on ultimate height. Archives of General Psychiatry, 45, 1131-1134. 

Methylphenidate, effects at different ages, 31.6 Methylthiotetrazole, 11.226 Mibefradil, drug interactions, 23.210 Midazolam, 15.112 Midodrine, 26.159... 

However, clinical results with compounds enhancing cholinergic function have not been overly convincing (272). In the case of tacriae, however, the beneficial therapeutic iadex was sufficient to justify regulatory approval ia several countries. Psychostimulants such as pemoline, amphetamine, procaine, and methylphenidate have failed to show cognitive enhancing effects ia patients with dementia, except possibly as iadirect consequences of mood elevation. 

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). 

Fig. 2-10. The effect of flow rate on the resolution of methylphenidate enantiomers on vancomycin CSP (250 x 4.6 mm). The mobile phase was methanol 1.0 % triethyl-ammonium acetate (95/5 v/v) pH 4.1 at ambient temperature (23 °C).

At low doses, both psychostimulants could theoretically stimulate tonic, extracellular levels of monoamines, and the small increase in steady state levels would produce feedback inhibition of further release by stimulating presynaptic autoreceptors. While this mechanism is clearly an important one for the normal regulation of monoamine neurotransmission, there is no direct evidence to support the notion that the doses used clinically to treat ADHD are low enough to have primarily presynaptic effects. However, alterations in phasic dopamine release could produce net reductions in dopamine release under putatively altered tonic dopaminergic conditions that might occur in ADHD and that might explain the beneficial effects of methylphenidate in ADHD. 

Psychostimulants. Figure 3 Effect of methylphenidate depending on baseline tonic (T) and phasic (P) dopamine levels. In a normal state only minimal changes are noted (which points to a rather low abuse potential). From a hypoactive state, methylphenidate increases both Tand P levels. However, this is much more true for the strongly lowered P tone. In contrast, in moderately hyperactive states and ADHD, T levels are increased and P levels are decreased, respectively, correlating with the baseline levels (adapted from [2]). 

Martin WR, Sloan JW, Sapira JD, et al Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12 245-258, 1971 McCormick TC Jr, McNeil TW Acute psychosis and Ritalin abuse. Tex State J Med... 

Psychostimulants (e.g., methylphenidate and dextroamphetamine with or without amphetamine) are the most effective agents in treating ADHD. Once the diagnosis of ADHD has been made, a stimulant medication should be used first line in treating ADHD (Fig. 39-1). Stimulants are safe and effective, with a response rate of 70% to 90% in patients with ADHD.3,13,14 Generally, a trial of at least 3 months on a stimulant is appropriate, and this includes dose titration to response... 

Initial response to short-acting stimulant formulations (e.g., methylphenidate and dextroamphetamine) is seen within 30 minutes and can last for 4 to 6 hours.13,14 This short duration of effect frequently requires that short-acting stimulant formulations be dosed at least twice daily, thus increasing the chance of missed doses and non-compliance. Further, patients using any stimulant formulation but especially shortacting formulations can experience a rebound effect of ADHD symptoms as the stimulant wears off.14... 

Chiat L. Reinforcing and subjective effects of methylphenidate in humans. Behav. Pharmacol. 5 281, 1994. 

The answer is a. (Hardman, p 22L Katzang, p L3L) Methylphenidate is similar to amphetamine and acts as a CN5 stimulant, with more pronounced effects on mental than on motor activities. It is effective in the treatment of narcolepsy and attention-deficit hyperactivity disorders. 

Amphetamines and methylphenidate have a fast onset of effect and durations of 3 to 4 hours and 6 to 10 hours, respectively, for excessive... 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

The (+)-enantiomer, DOV 21,947, is approximately twice as potent at NET and SERT as DOV 216,303. The minimum effective dose in both mouse tail suspension and rat FST models is 5mg/kg [87,88]. The (—)-enantiomer, DOV 102,677, is less potent than DOV 216,303 across all three transporters [89]. It is active in the FST in rats with a minimum effective dose of 20mg/kg. DOV 102,677 is as effective as methylphenidate in reducing the amplitude of the startle response in juvenile mice, without notably altering motor activity. It is reportedly under development for the treatment of alcohol abuse and alcoholism [68]. 

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