Anorectic effects

Finally, the actions of the so-called 5-HT releasing agent , if-fenfluramine, which is well known for its anorectic effects, should be mentioned here. This compound inhibits 5-HT uptake but its metabolite, if-norfenfluramine, increases 5-HT release as do high doses of (i-amphetamine. It is important to realise that this 5-HT release is independent of nerve impulses and the action of such compounds rests on their effects on the 5-HT transporters on the storage vesicles and terminal membrane. Once these drugs have been taken up into 5-HT neurons by the transporter, they cause 5-HT to leak out of its storage vesicles and, ultimately, to be extruded from the neuron by retrotransport (see below and Chapter 4 for further details). 

The results of behavioral studies reviewed are summarized in table 3. It is clear that a neurotoxic regimen of METH produced tolerance to the effects of subsequent injections of METH on either conditioned or unconditioned behaviors. The regimen of METH produced long-lasting depletions of DA in each of these studies. Similarly, repeated administration of fenfluramine also produced decreases in 5-HT and tolerance to the anorectic effects of fenfluramine. Repeated administration of MDMA to rats performing a DRL schedule resulted in sensitization to the effects of MDMA. This latter finding is interpreted as being due to the effects, MDMA on DA release, in... 

Kleven. M.S. Schuster, C.R. and Seiden. L.S. The effect of depletion of brain serotonin by repeated fenfluramine on neurochemical and anorectic effects of acute fenfluramine. J Pharmacol Exp Ther 246 1-7, 1988. 

Conversely, food intake and body weight are reduced by the selective cannabinoid CBl antagonist SR 141716. Tolerance developed to the anorectic effect of SR 141716 within 5 days of chronic treatment, but body weight remained low throughout 14 days of treatment. In contrast, chronic THC treatment (15 days) suppresses intake of food and water (Drewnowski and Grinker 1978). This effect is of short duration, with... 

Drugs with thyroid hormone activity, alone or with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects. 

Tolerance When tolerance to the anorectic effect develops, do not exceed recommended dose in an attempt to increase the effect rather, discontinue the drug. 

Tolerance to anorectic effects may develop within weeks cross-tolerance is almost universal... 

Serotonin has an effect on the hypothalamic control of pituitary function (see chapter 5), in central thermoregulation (attributed to the 5-HTj receptor), and in pain perception (probably the S-HTj receptor), where increased serotonergic function potentiates opiate analgesia. The administration of 5-HT reuptake inhibitors like fluoxetine increases the anorectic effect of 5-hydroxytryptamine and induces a selective suppression of nonprotein caloric intake in rats. The involvement of serotonin in endogenous psychiatric depression has been mentioned. 

The psychomotor stimulants, cocaine and D-amphetamine, are considered together because they share a similar psychopharmacological profile.19 20 Low to moderate doses of both drugs given acutely to nontolerant, nonanxious subjects produce increases in positive mood (euphoria), energy, and alertness. Experienced cocaine users were unable to distinguish between intravenous (IV) cocaine and D-amphetamine,21 and cross-tolerance between cocaine and D-amphetamine with respect to their anorectic effect has been demonstrated.22 Additionally, the toxic psychosis observed after days or weeks of continued use of both psychostimulants is very similar. The fully developed toxic syndrome, characterized by vivid auditory and visual hallucinations, paranoid delusions, and... 

Therapeutic uses Factors that limit the therapeutic usefulness of amphetamine include psychological and physiological dependence similar to those with cocaine, and the development of tolerance to the euphoric and anorectic effects with chronic use. [Note Less tolerance to the toxic CNS effects (for example, convulsions) develops.]... 

The conflict between the BGA and Eli Lilly went on for many years. On February 6, 1991, Hans Weber, representing Eli Lilly in Germany, wrote to Ray Fuller at Eli Lilly. He described a meeting held between Eli Lilly representatives and the BGA. Weber (as cited in Breggin, 1994) stated, The question was raised whether fluoxetine could be an amphetamine-like drug, which may explain its stimulating and anorectic effects (p. 3154). 

The additional anorectic effect of a candidate compound with a different primary indication does not represent a safety concern. In contrast, an orexigenic potential of a candidate compound, identified during... 

Cooper et al. (1990a, b) used non-deprived rats to study anorectic effects in a test of palatable food consumption and in nocturnal free-feeding. 

Caccia et al. (1993) studied the anorectic effect of D-fcnlluraminc in the marmoset (Callithrix jacchus). 

Caccia S, Anelli M, Fracasso C et al. (1993) Anorectic effect and brain concentrations of D-fenfluramine in the marmoset relationship to the in vivo and in vitro effects on serotonergic mechanisms. Naunyn Schmiedeberg s Arch Pharmacol... 

Cooper SJ, Dourish CT, Barber DJ (1990b) Reversal of the anorectic effect of (+)-fenfluramine in the rat by the selective cholecystokinin receptor antagonist MK-329. Br J Pharmacol 99 65-70... 

Cooper SJ, Francis J, Rusk IN (1990) The anorectic effect of SK F 38393, a selective dopamine D1 agonist a micro-structural analysis of feeding and related behavior. Psychopharmacology 100 182-187... 

Rouru J, Huuponen R, Pesonen U, Koulu M (1992) Subchronic treatment with metformin produces anorectic effect and reduces hyperinsulinemia in genetically obese Zucker rats. Life Sci 50 1813-1820... 

Compounds 696 and 697 are further examples for antihypertensive agents, in which a cyclopropylamino group is involved. Diuretic, hypnotic and anorectic effects have been claimed for 697, too . Aminocyclopropanes with tranquillizing properties or as part of a tranquillizing system have been reported. Antiinflammatory activity was found for compounds 698 and 699 for further examples see Refs 77, 391. Analgesic effectiveness has been established for some... 

While tolerance to the anorectic effects of fenfluramine appears to set in after 6-12 months, tolerance to its adverse effects is much more rapid in onset (90). 

Both cocaine and the amphetamines are sympathomimetic drugs that increase heart rate, blood pressure, and respiratory rate, and cause pupil dilation. Other effects of stimulants include anorectic effects, increased alertness and arousal, mood elevation, and at low doses, enhanced performance on a variety of tasks. 

Anorectic effects Causing one to lose appetite suppression of eating (Chapter 6). 

Use in Obesity. As noted earlier, many of the psychostimulants have also been used as anorectics (anorexics anorexigenics), that is, as appetite suppressants. A few of them are still useful in this regard, but the high abuse potential of psychostimulants, coupled with the development of tolerance to their anorectic effects, has meant that prescribing psychostimulants for weight control has generally fallen into disfavor. 

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