Effects of fenfluramine and phentermine (fen-phen) on dopamine and serotonin release in rat striatum: in vivo microdialysis study in conscious animals. Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey. Effects of fluoxetine, phentermine, and venlafaxine on pulmonary arterial pressure and electrophysiology. Ionamin online references

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Brain Res. 1998 Nov 30;813(1):67-72.
Effects of fenfluramine and phentermine (fen-phen) on dopamine and serotonin release in rat striatum: in vivo microdialysis study in conscious animals.

Balcioglu A, Wurtman RJ.

Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, E25-604, Cambridge, MA 02139, USA.

We measured the effects of acute or chronic administration of fenfluramine and phentermine, alone or in combination, on brain dopamine and serotonin release into striatal dialysates of freely moving rats. Samples collected every 30 min were assayed in a single run by high-pressure liquid chromatography. Acute or chronic administration of fenfluramine (1 mg/kg, i.p.) did not significantly change dopamine concentrations in rat striatal dialysates, but increased those of serotonin by 182% (acute) and 124% (chronic). Phentermine (2 mg/kg, i.p.), on the other hand, significantly increased dopamine concentrations by 52% (acute) and 80% (chronic) without affecting those of serotonin. Administration of the drugs in combination (fenfluramine 1 mg/kg and phentermine 2 mg/kg) amplified the effects of each, increasing striatal dopamine concentrations by 209% (acute) and serotonin concentrations by 330% (acute) and 299% (chronic). Copyright 1998 Elsevier Science B.V.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9824670&dopt=Abstract

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J Pharmacol Exp Ther. 1999 Feb;288(2):550-60.
Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey.

Wojnicki FH, Rothman RB, Rice KC, Glowa JR.

Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9918558&dopt=Abstract

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Am J Physiol. 1999 Feb;276(2 Pt 1):L213-9.
Effects of fluoxetine, phentermine, and venlafaxine on pulmonary arterial pressure and electrophysiology.

Reeve HL, Nelson DP, Archer SL, Weir EK.

Department of Physiology, University of Alberta, Edmonton, Canada T6G 2R7.

The anorexic agents dexfenfluramine and fenfluramine plus phentermine have been associated with outbreaks of pulmonary hypertension. The fenfluramines release serotonin and reduce serotonin reuptake in neurons. They also inhibit potassium current (IK), causing membrane potential depolarization in pulmonary arterial smooth muscle cells. The recent withdrawal of the fenfluramines has led to the use of fluoxetine and phentermine as an alternative anorexic combination. Because fluoxetine and venlafaxine reduce serotonin reuptake, we compared the effects of these agents with those of phentermine and dexfenfluramine on pulmonary arterial pressure, IK, and membrane potential. Fluoxetine, venlafaxine, and phentermine caused minimal increases in pulmonary arterial pressure at concentrations < 100 microM but did cause a dose-dependent inhibition of IK. The order of potency for inhibition of IK at +50 mV was fluoxetine > dexfenfluramine = venlafaxine > phentermine. Despite the inhibitory effect on IK at more positive membrane potentials, fluoxetine, venlafaxine, and phentermine, in contrast to dexfenfluramine, had minimal effects on the cell resting membrane potential (all at a concentration of 100 microM). However, application of 100 microM fluoxetine to cells that had been depolarized to -30 mV by current injection elicited a further depolarization of >18 mV. These results suggest that fluoxetine, venlafaxine, and phentermine do not inhibit IK at the resting membrane potential. Consequently, they may present less risk of inducing pulmonary hypertension than the fenfluramines, at least by mechanisms involving membrane depolarization.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9950882&dopt=Abstract

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