Phentermine+fenfluramine produce cocaine-like discriminative cues. Exposure to crystalline silica or treatment with chlorphentermine increases vitamin E levels in rat alveolar lavage materials. Phentermine pretreatment antagonizes the cocaine-induced rise in mesolimbic dopamine. Ionamin online references

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Life Sci. 1996;59(20):PL303-8.
Phentermine+fenfluramine produce cocaine-like discriminative cues.

Schechter MD, McBurney D.

Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.

Drug discrimination studies were conducted in six male Sprague-Dawley rats trained to discriminate the interoceptive cues produced by 10 mg/kg cocaine in an effort to investigate if there is stimulus generalization to phentermine or phentermine + fenfluramine. Once having reached criterion performance, these rats were tested with lower doses of cocaine and generated a typical dose-response curve allowing for calculation of an ED50 value: 2.798 mg/kg. Testing of phentermine in doses of 1.25-5.0 mg/kg indicated generalization with the highest dose producing 80% cocaine-appropriate responding and allowing for an ED50 value of 2.356 mg/kg. When the phentermine doses were tested in combination 2.0 mg/kg fenfluramine, however, there was an increase in the discriminability of the highest phentermine dose and a slight decrease in the ED50 value of the combination. Thus, administration of phentermine + fenfluramine, having both dopamine-releasing and serotonin-releasing properties, respectively, may mimic the neurochemical activity by which cocaine acts in the central nervous system and may possibly allow for cocaine-like effects as these two drugs see increased use in obesity control.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8890951&dopt=Abstract

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J Toxicol Environ Health. 1996 Dec 6;49(5):511-23.
Exposure to crystalline silica or treatment with chlorphentermine increases vitamin E levels in rat alveolar lavage materials.

Miles PR, Bowman L, Reasor MJ.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.

Previous studies have shown that vitamin E may be an integral part of lung surfactant and may function to protect this material from oxidant damage. Therefore, we measured the vitamin E levels in alveolar lavage materials from rats exposed to crystalline silica or treated with chlorphentermine (CP), two treatments that are known to increase surfactant phospholipids (PL) by different mechanisms. Silica exposure leads to increased PL synthesis, and CP treatment causes a reduction in PL degradation. Two different silica preparations, HCL-washed and unwashed silica, were used because exposure to each of them leads to different degrees of phospholipidosis. Exposure to HCL-washed silica results in a more than 17-fold increase in lavage PL and protein levels and a 12.2-fold increase in the amount of vitamin E. Exposure to unwashed silica leads to an approximately 7-fold increase in PL and proteins and a 5.8-fold increase in lavage vitamin E. Following treatment of rats with CP, there is a 15- to 19-fold increase in lavage PL and proteins and a 13.6-fold increase in vitamin E. When the results are expressed as micrograms vitamin E per milligram of lavage PL or protein, there is not much difference between controls and each treatment group. Because surfactant synthesis occurs in the endoplasmic reticulum, we also measured vitamin E in lung microsomes. Both silica exposure and CP treatment also lead to 1.8- to 2.5-fold increases, respectively, in the lung microsomal levels of vitamin E. These results demonstrate that alveolar lavage vitamin E levels are elevated along with lavage PL and proteins, and lung microsomal vitamin E levels are increased following exposure of rats to silica or treatment of the animals with CP.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8968411&dopt=Abstract

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Neuroreport. 1996 Dec 20;8(1):7-9.
Phentermine pretreatment antagonizes the cocaine-induced rise in mesolimbic dopamine.

Rothman RB, Ayestas M, Baumann MH.

Clinical Psychopharmacology Section, DIR, NIDA, NIH, Baltimore, MD 21224, USA.

Coadministration of phentermine and fenfluramine has been used to treat cocaine dependence. Patients who relapse while receiving this treatment report diminished subjective effects of cocaine. Due to the importance of mesolimbic dopamine (DA) in mediating cocaine reinforcement, we hypothesized that phentermine might attenuate the effects of cocaine on DA transmission. We examined this proposal directly using in vivo microdialysis methods in the nucleus accumbens of awake rats. Rats were pretreated with saline or phentermine (1 mg kg-1, i.v.) and then challenged with cocaine (3 mg kg-1, i.v.). Phentermine alone caused a modest increase in DA, and phentermine pretreatment substantially reduced the cocaine-induced rise in extracellular DA. Phentermine did not alter the stimulatory effect of cocaine on 5-HT. Our findings suggest that phentermine may antagonize the subjective effects of cocaine in humans via a DA mechanism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9051742&dopt=Abstract

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