fenfluramine and Chemical Dependence studies

Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.
fenfluramine : A secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reuptake pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertension.

Research Excerpts

Excerpt	Relevance	Reference
"Fenfluramine has been used for a number of years as a short-term adjunct to diet in the management of obesity."	8.75	Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. ( Avery, GS; Brogden, RN; Pinder, RM; Sawyer, PR; Speight, TM, 1975)
"Smokers had a blunted prolactin response to fenfluramine compared with nonsmokers without any alcoholism or antisocial personality effects."	5.09	Cigarette smoking decreases the prolactin response to serotonergic stimulation in subgroups of alcoholics and controls. ( Anthenelli, RM; Maxwell, RA, 2000)
"Fenfluramine has been used for a number of years as a short-term adjunct to diet in the management of obesity."	4.75	Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. ( Avery, GS; Brogden, RN; Pinder, RM; Sawyer, PR; Speight, TM, 1975)
"Sixty male offenders with DSM-III-R personality disorders and 27 healthy staff controls were assessed using the Special Hospital Assessment of Personality and Socialisation (SHAPS), impulsivity and aggression ratings, d-fenfluramine challenge and plasma hormone concentrations."	3.71	Relationship between 5-HT function and impulsivity and aggression in male offenders with personality disorders. ( Anderson, IM; Deakin, JF; Dolan, M, 2001)
"003 to 3 milligrams per kilogram of body weight, failed to maintain self-injection behavior in rhesus monkeys that had initiated and maintained responding for cocaine or methohexital."	3.65	Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey. ( Tessel, RE; Woods, JH, 1974)
"Measures of subjective feeling used by five patients indicated that depression of mood occurred about four days after fenfluramine withdrawal."	3.65	Drugs of dependence though not of abuse: fenfluramine and imipramine. ( Brezinova, V; Briggs, M; Dunleavy, DL; Lewis, SA; Oswald, I, 1971)

Research

Studies (42)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Cumulative Percent Adherence of Medication Events Monitoring (MEMs) Cap

Timeframe	Studies, this research(%)	All Research%
pre-1990	26 (61.90)	18.7374
1990's	4 (9.52)	18.2507
2000's	10 (23.81)	29.6817
2010's	2 (4.76)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Suyama, JA	1
Sakloth, F	1
Kolanos, R	1
Glennon, RA	1
Lazenka, MF	1
Negus, SS	2
Banks, ML	2
Rothman, RB	2
Blough, BE	2
Baumann, MH	2
Ayala, ME	1
Johanson, CE	1
Uhlenhuth, EH	1
Kramer, K	1
Azmitia, EC	1
Whitaker-Azmitia, PM	1
Locke, KW	1
Levesque, TR	1
Nicholson, KL	1
Balster, RL	1
Buydens-Branchey, L	1
Branchey, M	1
Hudson, J	1
Rothman, M	1
Fergeson, P	1
McKernin, C	1
Gerra, G	2
Zaimovic, A	1
Ferri, M	1
Zambelli, U	1
Timpano, M	1
Neri, E	1
Marzocchi, GF	1
Delsignore, R	1
Brambilla, F	1
Rada, PV	1
Hoebel, BG	1
Lawless-Liday, C	1
Force, RW	1
Anthenelli, RM	1
Maxwell, RA	1
Dolan, M	2
Anderson, IM	1
Deakin, JF	1
Haney, M	1
Ward, AS	1
Foltin, RW	1
Deakin, WJ	1
Roberts, N	1
Anderson, I	1
Griffiths, RR	2
Brady, JV	1
Snell, JD	1
Bigelow, GE	1
Liebson, I	1
Kaliszak, J	1
Götestam, KG	3
Pinder, RM	1
Brogden, RN	1
Sawyer, PR	1
Speight, TM	1
Avery, GS	1
Dare, GL	1
Goldney, RD	1
Rosenvinge, HP	1
Levin, A	4
Goudie, AJ	1
Thornton, EW	1
Andersson, BE	1
Byrne, A	1
Fishbein, DH	1
Lozovsky, D	1
Jaffe, JH	1
Woods, JH	1
Tessel, RE	1
Oswald, I	4
Gunne, LM	1
Jorgensen, F	1
Greenwood, MH	1
Dykes, MH	1
Lewis, SA	1
Dunleavy, DL	1
Brezinova, V	1
Briggs, M	1
Hawks, DV	1
Harding, T	1
De Groot, JC	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Treatment With Lorcaserin for Cocaine Use: The TLC Study[NCT03192995]	Phase 2	22 participants (Actual)	Interventional	2018-01-01	Terminated (stopped due to FDA alert regarding study drug safety)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To evaluate the adherence of lorcaserin vs. placebo, the investigators measured adherence as the frequency of taking the study drug as measured by the number of MEMS cap openings (wireless medication monitoring devices that record each opening as a real-time medication event). Cumulative percent adherence was calculated by dividing the frequency of openings at a given time point divided by the number of days since baseline. (NCT03192995)
Timeframe: 12 weeks

Mean Percentage of Weekly Follow-up Visits of Randomized Study Participants

Intervention	percent adherence (Mean)
Experimental	51.6
Control	66.2

To determine the feasibility of retaining individuals on lorcaserin vs. placebo, the investigators have calculated the mean weekly percentage of follow-up visits of those randomized in the study (NCT03192995)
Timeframe: 12 weeks

Proportion of Self-reported Past Week Cocaine Use Among Lorcaserin and Placebo Groups at Baseline and at 12 Weeks

Intervention	mean percent of visit retention (Mean)
	Treatment Group	Control Group
Mean Percent of Weekly Follow-up Visits by Treatment and Control Arms	83	81

The outcome measure determines the proportion of self-reported past week cocaine use by Time-Line-Follow-back (TLFB) among lorcaserin and placebo groups at Baseline and at 12 weeks. (NCT03192995)
Timeframe: 12 weeks

Proportion of Urine-positive Samples With Cocaine Positivity Among Lorcaserin and Placebo Groups at Baseline and at Week 12

Intervention	Participants (Count of Participants)
	Proportion of self-reported weekly cocaine use by Time-Line-Follow-Up (TLFU) at baseline	Proportion of self-reported weekly cocaine use by TLFU at Week 12
Control	6	6
Experimental	12	7

The outcome measure determines the proportion of urine-positive samples with cocaine positivity among lorcaserin and placebo groups at Baseline and at Week 12 (NCT03192995)
Timeframe: Week 12

Article	Year
Dopamine/serotonin releasers as medications for stimulant addictions. Progress in brain research, 2008, Volume: 172 Topics: Animals; Behavior, Addictive; Central Nervous System Stimulants; Cocaine; Dopamine; Dopamine Agents;	2008
Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs, 1975, Volume: 10, Issue:4 Topics: Adult; Age Factors; Analgesics; Anticonvulsants; Appetite Depressants; Body Temperature; Central Ner	1975
[Fenfluramine and drug dependence]. Ugeskrift for laeger, 1973, Jan-29, Volume: 135, Issue:5 Topics: Appetite Depressants; Fenfluramine; Humans; Obesity; Psychoses, Substance-Induced; Substance-Related	1973
[Side effects associated with prolonged use of fenfluramine]. La Vie medicale au Canada francais, 1973, Volume: 2, Issue:3 Topics: Depersonalization; Diarrhea; Fatigue; Fenfluramine; Humans; Libido; Sleep; Substance-Related Disorde	1973

Article	Year
Serotonergic function in cocaine addicts: prolactin responses to sequential D,L-fenfluramine challenges. Biological psychiatry, 1999, May-15, Volume: 45, Issue:10 Topics: Administration, Oral; Adult; Alcoholism; Child of Impaired Parents; Cocaine-Related Disorders; Fathe	1999
Cigarette smoking decreases the prolactin response to serotonergic stimulation in subgroups of alcoholics and controls. Alcoholism, clinical and experimental research, 2000, Volume: 24, Issue:7 Topics: Adolescent; Adult; Alcoholism; Analysis of Variance; Chi-Square Distribution; Fenfluramine; Humans;	2000
Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers. Biological psychiatry, 1989, Apr-15, Volume: 25, Issue:8 Topics: Adult; Aggression; Fenfluramine; Humans; Hydrocortisone; Impulsive Behavior; Male; Prolactin; Psycho	1989
Subjective effects of two anorexigenic agents fenfluramine and AN 448 in amphetamine-dependent subjects. The British journal of addiction to alcohol and other drugs, 1972, Volume: 67, Issue:1 Topics: Adult; Amphetamine; Appetite Depressants; Fenfluramine; Humans; Imidazoles; Male; Substance-Related	1972
Evaluation of three anorexiants. Clortermine hydrochloride (voranil), fenfluramine hydrochloride (pondimin), and mazindol (sanorex). JAMA, 1974, Oct-14, Volume: 230, Issue:2 Topics: Adolescent; Adult; Age Factors; Appetite Depressants; Clinical Trials as Topic; Depression; Diet, Re	1974
Drugs and sleep. British medical journal, 1968, Jun-01, Volume: 2, Issue:5604 Topics: Appetite Depressants; Clinical Trials as Topic; Diethylpropion; Fenfluramine; Humans; Phenethylamine	1968

Article	Year
Abuse-Related Neurochemical Effects of Para-Substituted Methcathinone Analogs in Rats: Microdialysis Studies of Nucleus Accumbens Dopamine and Serotonin. The Journal of pharmacology and experimental therapeutics, 2016, Volume: 356, Issue:1 Topics: Amphetamine; Animals; Behavior, Animal; Designer Drugs; Dopamine; Dopamine Plasma Membrane Transport	2016
Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure-Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs. Current topics in behavioral neurosciences, 2017, Volume: 32 Topics: Amphetamine; Animals; Behavior, Animal; Dopamine Plasma Membrane Transport Proteins; Fenfluramine; H	2017
Brain serotonin, psychoactive drugs, and effects on reproduction. Central nervous system agents in medicinal chemistry, 2009, Volume: 9, Issue:4 Topics: Affect; Amphetamine-Related Disorders; Animals; Biological Clocks; Brain; Cognition Disorders; Depre	2009
Drug preferences in humans. Federation proceedings, 1982, Volume: 41, Issue:2 Topics: Adult; Arousal; Dextroamphetamine; Diazepam; Emotions; Fenfluramine; Humans; Reinforcement, Psycholo	1982
In vitro release of [3H]5-hydroxytryptamine from fetal and maternal brain by drugs of abuse. Brain research. Developmental brain research, 1994, Mar-18, Volume: 78, Issue:1 Topics: 3,4-Methylenedioxyamphetamine; Animals; Brain; Brain Chemistry; Cocaine; Designer Drugs; Female; Fen	1994
Dexfenfluramine lacks amphetamine-like abuse potential. Progress in neuro-psychopharmacology & biological psychiatry, 1996, Volume: 20, Issue:6 Topics: Amphetamine; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Fenfluramine; Macaca mulat	1996
Long-lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans. Biological psychiatry, 2000, Jan-15, Volume: 47, Issue:2 Topics: Adolescent; Adult; Exploratory Behavior; Fenfluramine; Hallucinogens; Hostility; Humans; Hydrocortis	2000
Supraadditive effect of d-fenfluramine plus phentermine on extracellular acetylcholine in the nucleus accumbens: possible mechanism for inhibition of excessive feeding and drug abuse. Pharmacology, biochemistry, and behavior, 2000, Volume: 65, Issue:3 Topics: Acetylcholine; Animals; Appetite Depressants; Dopamine; Drug Synergism; Feeding Behavior; Fenflurami	2000
Lessons from the fenfluramines: antiobesity medications are frequently misused. The Annals of pharmacotherapy, 2000, Volume: 34, Issue:3 Topics: Anti-Obesity Agents; Appetite Depressants; Fenfluramine; Heart Valve Diseases; Humans; Substance-Rel	2000
Relationship between 5-HT function and impulsivity and aggression in male offenders with personality disorders. The British journal of psychiatry : the journal of mental science, 2001, Volume: 178 Topics: Adult; Aggression; Fenfluramine; Humans; Hydrocortisone; Impulsive Behavior; Male; Personality Disor	2001
Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated smoked cocaine in humans. Drug and alcohol dependence, 2001, Sep-01, Volume: 64, Issue:1 Topics: Adult; Analysis of Variance; Bromocriptine; Crack Cocaine; Fenfluramine; Humans; Hydrocortisone; Mal	2001
Serotonergic and cognitive impairment in impulsive aggressive personality disordered offenders: are there implications for treatment? Psychological medicine, 2002, Volume: 32, Issue:1 Topics: Adult; Aggression; Analysis of Variance; Cluster Analysis; Fenfluramine; Humans; Hydrocortisone; Imp	2002
Appetite suppressants as agonist substitution therapies for stimulant dependence. Annals of the New York Academy of Sciences, 2002, Volume: 965 Topics: Aminorex; Animals; Appetite Depressants; Dopamine; Fenfluramine; Male; Methamphetamine; Microdialysi	2002
Relationship between anorectic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability. Biological psychiatry, 1978, Volume: 13, Issue:2 Topics: Animals; Appetite; Appetite Depressants; Chlorphentermine; Cocaine; Dextroamphetamine; Diethylpropio	1978
Therapeutic self-medication as a context for drug abuse research. NIDA research monograph, 1978, Issue:20 Topics: Adult; Body Weight; Dextroamphetamine; Drug Prescriptions; Female; Fenfluramine; Humans; Male; Metha	1978
The discriminative properties of amphetamine analogues tested in self-administering rats under maintained stimulus control. Addictive behaviors, 1977, Volume: 2, Issue:1 Topics: Amphetamines; Animals; Conditioning, Operant; Dextroamphetamine; Diethylpropion; Discrimination, Psy	1977
Fenfluramine abuse. The Medical journal of Australia, 1976, Oct-02, Volume: 2, Issue:14 Topics: Adolescent; Adult; Female; Fenfluramine; Humans; Male; Substance-Related Disorders	1976
Letter: Abuse of fenfluramine. British medical journal, 1975, Mar-29, Volume: 1, Issue:5960 Topics: Adult; Drug Tolerance; Female; Fenfluramine; Humans; Substance-Related Disorders	1975
The non-medical misuse of fenfluramine by drug-dependent young South Africans. Postgraduate medical journal, 1975, Volume: 51 Suppl 1 Topics: Adolescent; Adult; Fenfluramine; Humans; Male; South Africa; Substance-Related Disorders	1975
Effects of drug experience on drug induced conditioned taste aversions: studies with amphetamine and fenfluramine. Psychopharmacologia, 1975, Oct-14, Volume: 44, Issue:1 Topics: Animals; Avoidance Learning; Body Weight; Choice Behavior; Conditioning, Psychological; Dextroamphet	1975
Assessment of reinforcing properties of amphetamine analogues in self-administering rats. Postgraduate medical journal, 1975, Volume: 51 Suppl 1 Topics: Amphetamine; Animals; Behavior, Animal; Diethylpropion; Fenfluramine; Humans; Male; Phenmetrazine; R	1975
Probing dexfenfluramine. The British journal of psychiatry : the journal of mental science, 1992, Volume: 161 Topics: Adult; Brain; Female; Fenfluramine; Humans; Male; Middle Aged; Substance-Related Disorders	1992
Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey. Science (New York, N.Y.), 1974, Sep-20, Volume: 185, Issue:4156 Topics: Animals; Behavior, Animal; Body Weight; Cocaine; Conditioning, Operant; Dose-Response Relationship,	1974
Sleep. Experimental medicine and surgery, 1969, Volume: 27, Issue:1-2 Topics: Amobarbital; Appetite Depressants; Barbiturates; Dreams; Electroencephalography; Fenfluramine; Fluor	1969
The pattern of drug-taking among drug-dependent South African national servicemen. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1972, Nov-04, Volume: 46, Issue:44 Topics: Adolescent; Adult; Age Factors; Alcoholism; Amphetamine; Barbiturates; Cannabis; Cocaine; Datura str	1972
Drug-taking patterns in the National Service. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1973, Mar-10, Volume: 47, Issue:10 Topics: Cannabis; Fenfluramine; Heroin Dependence; Humans; Lysergic Acid Diethylamide; Military Medicine; So	1973
Abuse of fenfluramine. British medical journal, 1973, Apr-07, Volume: 2, Issue:5857 Topics: Depression; Euphoria; Fenfluramine; Humans; Male; Perception; Substance-Related Disorders; Thermosen	1973
Drugs of dependence though not of abuse: fenfluramine and imipramine. British medical journal, 1971, Jul-10, Volume: 3, Issue:5766 Topics: Adult; Appetite Depressants; Body Weight; Depression; Dreams; Female; Fenfluramine; Fluorine; Humans	1971
Unusual effect of fenfluramine. British medical journal, 1969, Dec-27, Volume: 4, Issue:5686 Topics: Appetite Depressants; Central Nervous System; Female; Fenfluramine; Fluorine; Humans; Male; Phenethy	1969
Unusual effect of fenfluramine. British medical journal, 1970, Jan-24, Volume: 1, Issue:5690 Topics: Appetite Depressants; Fenfluramine; Fluorine; Humans; Phenethylamines; Substance-Related Disorders	1970
Fenfluramine dependence. British medical journal, 1971, Jul-31, Volume: 3, Issue:5769 Topics: Adult; Appetite Depressants; Depression; Female; Fenfluramine; Fluorine; Humans; Obesity; Phenethyla	1971
A survey of the usage of amphetamines in parts of the Sidney community. The Medical journal of Australia, 1968, May-11, Volume: 1, Issue:19 Topics: Amphetamine; Australia; Diethylpropion; Fenfluramine; Humans; Phenmetrazine; Sleep; Substance-Relate	1968

fenfluramine and Chemical Dependence