Sympathomimetic Amines: Actions and Uses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Amphetamine was found to promote weight loss when used in patients suffering from narcolepsy (prolonged bouts of sleepiness). Dexamphetamine (DexedrineR) has been used in the treatment of obesity, the weight loss being due to suppression of appetite rather than an effect on energy expenditure. Its effect is short-lived since tolerance develops and there are risks of hypertension and sleep disturbances. Amphetamine and related agents [phentermine (Ionamin, Duramine, FastinUS), diethylpropion (Tenuate DospanR), pheadimetrazine (PlegineUS), benzphetamine (DidrexUS), methamphetamine (DesoxynUS)] have psychostimulant properties and have potential for abuse and habituation. They have therefore been largely replaced by non-stimulant derivatives such as fenfluramine (PonderaxR) and its dextro isomer, dexfenfluramine (AdifexR). Whereas amphetamines are indirectly acting sympathomimetic amines releasing noradrenaline from nerve endings, fenfluramine releases 5-HT and is sedative rather than stimulant; in fact depression is a potential adverse effect. Mazindol (TeronacUK, MazanorUS) is a tricyclic antidepressant, structurally unrelated to amphetamine, which is an inhibitor of neuronal uptake. It supresses appetite and will interact with antihypertensives (eg neurone blockers).
Intestinal Pharmacomanometry: Evidence for Two Antagonistic Dopaminergic Mechanisms in the Human
Fuad Lechin, Bertha van der Dijs in Neurochemistry and Clinical Disorders: Circuitry of Some Psychiatric and Psychosomatic Syndromes, 2020
Clonazepam, an anticonvulsant drug, has been shown to be very useful in controlling affective and schizoaffective disorders.34 Doses as low as 0.25 mg b.i.d. are effective in treating vertigo, insomnia, and anxiety (unpublished results). Higher doses eliminated psychotic schizoaffective disorder patients.34 Bromocriptine is a valuable tool in the treatment of hyperprolactinemia and Parkinson’s disease, while mazindol is a new anorexic agent. An understanding of the intimate mechanisms of action of all these drugs could explain the failure or the paradoxical effects they can induce. d-Amphetamine, methylphenidate, nomifensine, l-dopa, etc. increase the availability of dopamine at the synaptic cleft, and thus act as stimulating agents. In all these cases, the agonistic action of dopamine decreases as time elapses. According to Martress et al.,20 inhibitory impulses of DA release and synthesis arising from the stimulation of presynaptic (autoreceptors) and postsynaptic DA receptors by an augmented dopamine at the synapsis are the most generally accepted explanations for the decreasing effects of the drug. In addition, it has been shown recently that after sustained stimulation DA receptors may become hyposensitive to the action of DA agonists; this might result in a decrease of the therapeutic effect in Parkinson patients treated with L-dopa or bromocriptine. However, there is a large body of experimental evidence demonstrating that DA agonists in low doses lose, at least partly, their ability to inhibit DA release. Therefore, their postsynaptic effects are enhanced by the participation of endogenous dopamine, leading to an increased therapeutic response.
Pulmonary hypertension induced by drugs and toxins
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Mazindol is a sympathomimetic amine, similar to amphetamine (see Fig. 29.2). We found only a single case report of PAH diagnosed 12 months after discontinuing mazindol that had been taken for 10 weeks.44
Reviewing the role of emerging therapies in the ADHD armamentarium
Published in Expert Opinion on Emerging Drugs, 2021
Ann C. Childress, Nathalie Beltran, Carl Supnet, Margaret D. Weiss
MPH is the most widely used prescription medication for ADHD and is frequently misused by high school and college students [48,156,157]. Although LDX could be said to have abuse-deterrent qualities as a prodrug with no activity of the parent compound until metabolically activated, it is a DEA Schedule II drug [158]. Several IR AMPH abuse-deterrent formulations are in development and will be a welcome addition to available treatments. AR-19 (racemic AMPH) is closest to being approved by the FDA in the U.S. The abuse-deterrent d-MPH formulation KP484, which is an ER prodrug of dMPH, is earlier in development and the DURECT ER MPH has not been studied in the U.S. A combination MPH plus naltrexone is also in development, but its potential indication is ADHD + substance use disorder. Mazindol was previously labeled as a DEA Schedule IV drug. Its abuse potential is unclear. It is unknown what scheduling it will receive should it be approved for the treatment of ADHD.
Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD
Published in Expert Review of Neurotherapeutics, 2019
Fatuma Nageye, Samuele Cortese
The results of the RCT on Mazindol (NCT02808104 [22]) were published as full-text study [47]. In this phase II, randomized, double-blind, placebo-controlled 6-week trial, 85 adults with ADHD were randomized to Mazindol (1–3 mg/day) or placebo. At day 42, Mazindol was significantly better than placebo in reducing the severity of ADHD symptoms measured with the ADHD-RS-DSM5 (primary outcome) with a large ES (= 1.09). Overall, 42.9% of the participants randomized to Mazindol, vs 11.9% of those assigned to placebo, had a CGI-I score of 1 or 2 (secondary outcome). No deaths or serious AEs were reported. Overall, 42%, 38%, and 57% of the participants receiving Mazindol CR 1, 2, and 3 mg QD and 21%, 12%, and 36% of the patients receiving placebo, respectively, had AEs. Dry mouth, nausea, fatigue, increased heart rate, decreased appetite, and constipation were more frequent in the Mazindol group vs the placebo group. Mazindol was associated with minimal average increase in diastolic and systolic blood pressures (~3–6 mmHg) and heart rate (7.5–11 bpm). No significant changes in QTcF, PR interval, or QRS complex were noted. There were no remarkable alterations on physical examination, hematology, serum chemistry, or urinalysis values from baseline to day 42 between Mazindol CR and placebo. By day 42, participants randomized to Mazindol presented with a mean weight loss of 1.73 kg (range −9.6 to +3.7).
Update on treatment for idiopathic hypersomnia
Published in Expert Opinion on Investigational Drugs, 2018
Elisa Evangelista, Régis Lopez, Yves Dauvilliers
In two retrospective series, dextro-amphetamine has been reported to improve EDS in IH, as assessed by a reduction in ESS score [6,27]. However, because of its potentially serious side effects, especially on cardiovascular system and psychiatric area, the French consensus considered this drug as last-line therapy in IH. In a multicentric retrospective trial, mazindol provided an improvement of EDS with reduction of 4.8 ± 4.7 points of ESS score in patients with IH refractory to conventional stimulants with a good risk-benefit ratio in 84% patients [31]. Mazindol is a potent tricyclic non-amphetamine stimulant that was available in France but no longer marketed currently.
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