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Obesity Research Nov 1995Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives... (Review)
Review
Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
Topics: Adrenergic Agents; Appetite Depressants; Benzocaine; Drug Therapy, Combination; Ephedrine; Fenfluramine; Humans; Obesity; Phentermine; Phenylpropanolamine; Serotonin Agents
PubMed: 8697049
DOI: 10.1002/j.1550-8528.1995.tb00218.x -
Current Topics in Behavioral... 2017Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because...
Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g., locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed "synthetic cathinones", and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i.e., as substrates) or reuptake inhibitors (i.e., as transport blockers), it has now become possible to better examine their SAR and even their quantitative SAR (QSAR), in a more effective and systematic manner. An SAR picture is beginning to emerge, and key structural features, such as the nature of the terminal amine, the size of the α-substituent, stereochemistry, and the presence and position of aromatic substituents, are being found to impact action (i.e., as releasing agents or reuptake inhibitors) and transporter selectivity.
Topics: Adrenergic Uptake Inhibitors; Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Humans; Phenylpropanolamine; Propiophenones; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship; Substance-Related Disorders
PubMed: 27830576
DOI: 10.1007/7854_2016_41 -
Trials Apr 2023Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive...
TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH): a study protocol for a multicenter, double-blinded, randomized, 3-arm trial to evaluate the multisystem effects of pharmacologic treatment strategies for urgency-predominant urinary incontinence in ambulatory older women.
BACKGROUND
Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.
METHODS
The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.
DISCUSSION
The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.
Topics: Humans; Female; Middle Aged; Aged; Tolterodine Tartrate; Muscarinic Antagonists; Urinary Bladder, Overactive; Quality of Life; Prospective Studies; Urinary Incontinence; Cholinergic Antagonists; Adrenergic Agonists; Treatment Outcome; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37085880
DOI: 10.1186/s13063-023-07279-z -
CMAJ : Canadian Medical Association... Mar 2001
Topics: Canada; Chemistry, Pharmaceutical; Female; Humans; Hypertension; Phenylpropanolamine; Stroke; United States; United States Food and Drug Administration
PubMed: 11258207
DOI: No ID Found -
Obesity (Silver Spring, Md.) Mar 2008At any one time large numbers of people are attempting to control their weight. Women are the principal consumers of weight-control programs. Their options, outside the... (Review)
Review
At any one time large numbers of people are attempting to control their weight. Women are the principal consumers of weight-control programs. Their options, outside the prescription drug market and surgical treatment, include diets and diet books, exercise alone or with supervision in exercise facilities, dietary supplements, group programs, doctors, dietitians, psychologists, and other health-care professionals. Non-prescription products available to help people control their weight cover a wide range, including herbal dietary supplements, diet drinks and portion-controlled foods, meal replacements, and low-carbohydrate diets and foods. The introduction of orlistat as an over-the-counter (OTC) product will provide the only Food and Drug Administration (FDA)-approved product for weight loss currently in that category since phenylpropanolamine (PPA) was withdrawn by the FDA. The FDA approval process is considerably more expensive than allowing untested herbal supplements to be marketed without testing, but the added safety evaluation by the FDA will reduce the risk of disastrous outcomes that have plagued many approaches to weight control. Support for a place for orlistat as an OTC product includes the inadequacy of current programs, empowerment of the public, lower cost, and bringing pharmacists into weight-control programs. The downside includes improper use of OTC orlistat that may not result in achieving individual expectations.
Topics: Anti-Obesity Agents; Body Image; Body Weight; Books; Chronic Disease; Delivery of Health Care; Diet, Carbohydrate-Restricted; Drug Approval; Female; Food, Formulated; Humans; Lactones; Life Expectancy; Male; Nonprescription Drugs; Obesity; Orlistat; Plant Preparations; Prejudice; Quality of Life; Recurrence; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 18239604
DOI: 10.1038/oby.2007.100 -
The New England Journal of Medicine Dec 2000Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to...
BACKGROUND
Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study.
METHODS
Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient.
RESULTS
There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants.
CONCLUSIONS
The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.
Topics: Adolescent; Adult; Appetite Depressants; Case-Control Studies; Cerebral Hemorrhage; Common Cold; Cough; Female; Humans; Male; Middle Aged; Nasal Decongestants; Phenylpropanolamine; Risk Factors; Subarachnoid Hemorrhage
PubMed: 11117973
DOI: 10.1056/NEJM200012213432501 -
The Cochrane Database of Systematic... May 2023Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic... (Review)
Review
BACKGROUND
Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006.
OBJECTIVES
To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.
Topics: Adult; Humans; Cholinergic Antagonists; Quality of Life; Tolterodine Tartrate; Urinary Bladder, Overactive; Systematic Reviews as Topic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37160401
DOI: 10.1002/14651858.CD003781.pub3 -
Chembiochem : a European Journal of... Jul 2021We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %)...
We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-β-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.
Topics: Alanine Dehydrogenase; Alcohol Dehydrogenase; Alcohols; Biocatalysis; Oxidation-Reduction; Phenylpropanolamine; Stereoisomerism; Styrenes; Transaminases
PubMed: 33880862
DOI: 10.1002/cbic.202100123 -
The American Journal of Managed Care Mar 2001Overactive bladder (OAB), the symptom complex of urinary urgency and frequency with or without urge incontinence, affects the lives of millions of Americans. In recent... (Review)
Review
Overactive bladder (OAB), the symptom complex of urinary urgency and frequency with or without urge incontinence, affects the lives of millions of Americans. In recent years, more successful treatment options have emerged as advances have been made in understanding the pathophysiologic processes underlying OAB symptoms. However, because most therapeutic modalities for OAB are aimed at symptom resolution, rather than the treatment of distinct pathologic entities, a basic evaluation is required for all patients to establish whether existing (and treatable) pathologic processes are present. In the absence of these processes, symptom relief is both the objective and the outcome used to judge the efficacy of a specific modality. The type of therapy recommended for OAB may depend on several factors including age, existing behavioral patterns, estrogen status, degree of motivation, environmental surroundings, presence of other coexisting urinary symptoms, family support, and patient expectations. This article focuses on methods of identifying patients with OAB, and the role of developing strategies in treating this common disorder.
Topics: Aged; Algorithms; Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Quality Assurance, Health Care; Tolterodine Tartrate; United States; Urinary Incontinence
PubMed: 11261408
DOI: No ID Found -
British Journal of Clinical Pharmacology Aug 19811 In a double-blind cross-over study, nine healthy male students received placebo, brompheniramine 12 mg), carbinoxamine (12 mg), clemastine (1 mg), and... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 In a double-blind cross-over study, nine healthy male students received placebo, brompheniramine 12 mg), carbinoxamine (12 mg), clemastine (1 mg), and phenylpropanolamine (50 mg) orally. Three doses of each drug were given: at 08.30 h and 21.00 h on the first day of treatment and at 08.30 h on the following day. 2 Psychomotor skills and subjective feelings were recorded before and 2, 6 and 12 h after the first dose on day 1 as well as before and 2 and 6 h after the third dose on day 2. Subjective appraisals of sleep were requested on the morning of day 2. 3 All antihistamines tended to cause subjective drowsiness on the first day of treatment. Drowsiness was felt for a maximum of 2 h after carbinoxamine, 6 h after brompheniramine, and 12 h after clemastine. In contrast to antihistamines, phenylpropanolamine made subjects more alert and quick witted. Tolerance to the antihistamine-induced drowsiness developed on the second day. 4 Divided attention, tracking, speed anticipation and sleep were not affected by any drug. Carbinoxamine slowed reactions 2 h after the first dose, but no impairment was measured in objective tests after brompheniramine or clemastine. 5 Phenylpropanolamine improved reaction speed and reaction accuracy and enhanced flicker recognition throughout the study. Phenylpropanolamine plasma levels and improvement in flicker fusion test results correlated with each other on day 2. 6 The results suggest that phenylpropanolamine and the antihistamines studied are comparatively harmless to psychomotor performance and driving skills.
Topics: Adult; Attention; Double-Blind Method; Histamine H1 Antagonists; Humans; Male; Motor Activity; Phenylpropanolamine; Psychiatric Status Rating Scales; Reaction Time; Sleep
PubMed: 6118170
DOI: 10.1111/j.1365-2125.1981.tb01198.x