Chlorphentermine-induced changes of the peripheral vestibular sense organ of the rat. Role of age in amphiphilic drug-induced pulmonary morphological and metabolic responses. Effect of chlorphentermine on the pulmonary disposition of 5-hydroxytryptamine in the isolated perfused rabbit lung. Ionamin online references

Ionamin online research references

Acta Otolaryngol. 1983 Nov-Dec;96(5-6):421-8.
Chlorphentermine-induced changes of the peripheral vestibular sense organ of the rat.

Bichler E, Anniko M.

Chronic feeding of chlorphentermine to young rats induces an accumulation of electron dense conglomerates and vacuoles in intraepithelial afferent nerve fibres of maculae and cristae in the vestibular part of the inner ear. In spite of the fact that preterminal parts of axons are severely swollen due to this accumulation, the nerve terminals maintain their normal size but can sometimes contain inclusions. Efferent fibres always remain free of these changes. Sensory cells, vestibular ganglion cells and occasionally supporting cells contain lamellar and crystalloid-like inclusions which disappear when the treatment is interrupted. After a long-term feeding break the nerve fibre inclusions disappear. A few swollen distended morphologically empty preterminals remain. The preference of inclusion body accumulation in afferent neurons may indicate an especially high lipid turnover in this part of the hair cell innervation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6138918&dopt=Abstract

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Fed Proc. 1984 Aug;43(11):2592-6.
Role of age in amphiphilic drug-induced pulmonary morphological and metabolic responses.

Kacew S.

The morphological and metabolic responsiveness of pulmonary tissue to amphiphilic agents is dependent on age. Daily oral administration of chlorphentermine (60 mg/kg) for 1 wk produced an accumulation of phospholipid-rich hypertrophic macrophages in pulmonary alveoli accompanied by an increase in relative lung weight and elevation in levels of phosphatidylcholine (PC), sphingomyelin (S), phosphatidylserine (PS) plus phosphatidylinositol (PI), phosphatidylethanolamine (PE) plus phosphatidylglycerol (PG), and total phospholipid (TPL) in newborn rats. Chlorcyclizine treatment (60 mg . kg-1 . day-1) for 1 wk also resulted in an accumulation of hypertrophic macrophages and an increase in both TPL and PC levels in newborn lung. However, unlike chlorphentermine, the chlorcyclizine-stimulated increase in pulmonary cells was associated with no marked change in relative lung weight and levels of S, PG plus PE, and PS plus PI. Phenobarbital (30 mg/kg) reduced the chlorphentermine-induced (60 mg/kg) effect on neonatal relative lung weight, accumulation of hypertrophic macrophages, and phospholipid levels. Withdrawal from drug treatment for 2 wk in newborns previously given chlorphentermine for 7 days resulted in a disappearance of pulmonary hypertrophic macrophages and a return of TPL levels to control values. Our data support the view that age plays a role in the observed amphiphilic drug-induced morphological and metabolic responses in rat lung.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6146538&dopt=Abstract

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Am Rev Respir Dis. 1980 Dec;122(6):891-8.
Effect of chlorphentermine on the pulmonary disposition of 5-hydroxytryptamine in the isolated perfused rabbit lung.

Angevine LS, Mehendale HM.

It has been postulated that chlorphentermine (CP), as well as other drugs known to accumulate and to induce morphologic changes in lung tissue, might affect the uptake and metabolism of the endogenous vasopressor amine, 5-hydroxytryptamine (5-HT). The uptake and metabolism of [14C]5-HT was followed in artificially ventilated, isolated perfused rabbit lung preparations using erythrocyte-free perfusate with an initial 5-HT concentration of 5 microgram/100 ml. Samples of the perfusate were analyzed for total radioactivity, metabolites, and the parent compound. Preloading the lungs with 25 or 30 mumoles of CP significantly decreased the formation of 5-hydroxyindolacetic acid (5-HIAA) to 56% and 34% of the control value, respectively. These experiments indicated that decreased pulmonary metabolism of 5-HT by CP might be mediated via a dual effect of hindered uptake and inhibition of metabolism. In experiments designed to examine the effect on uptake by blocking 5-HT metabolism, CP significantly decreased 5-HT uptake by lungs preloaded with pargyline. In other experiments designed to examine the effect of CP on 5-HT metabolism, CP (0.3 mM) significantly inhibited 5-HT metabolism by 60% in in vitro incubations of rabbit lung homogenates. These experiments provided evidence that CP significantly decreases the pulmonary uptake and metabolism of 5-HT. Decreased pulmonary 5-HT clearance may bear a causal relation to the drug-induced pulmonary hypertension observed with chronic CP treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6161572&dopt=Abstract

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