Effects of chlorphentermine and phentermine on the pulmonary disposition of 5-hydroxytryptamine in the rat in vivo
This study was designed to examine whether chlorphentermine (CP) affects pulmonary disposition of 5-hydroxytryptamine (5-HT) in rat in vivo. Further, the effects of CP were compared with those of phentermine (P), the nonchlorinated congener. The right jugular vein and left carotid artery of male Sprague-Dawley rats were cannulated and fresh saline solution containing 150 micrograms indocyanine green and a mixture of labeled and unlabeled 5-HT was injected into the jugular vein, and arterial blood samples were collected for 20 s. In order to compare the effect of CP and P on pulmonary disposition of 5-HT, 2.6 nmol (/sup 14/C)-5-HT was employed for in vivo single-pass experiments. Each animal was used for 2 in vivo single-pass experiments. After the first experiment, which served as a control, animals received an indicated dose of CP or P, to commence the second ''drug-treated'' in vivo experiment. Pulmonary clearance of 5-HT was inhibited by prior administration of CP (1 mg/kg) by 42%, whereas at the highest dose (20 mg/kg) P inhibited 5-HT clearance by only 25%. Pulmonary accumulation of CP was greater than P at higher doses, and the inhibition of 5-HT clearance correlated with the pulmonary accumulation of these drugs. In addition to the in vivo demonstration of the CP inhibition of pulmonary clearance of 5-HT in the rat, these studies also demonstrate a higher affinity of the lung tissue for CP than for P and a greater propensity for the impairment of pulmonary 5-HT clearance.
- Research Organization:
- Univ. of Mississippi Medical Center, Jackson
- OSTI ID:
- 5019158
- Journal Information:
- Am. Rev. Respir. Dis.; (United States), Vol. 127:6
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
BIOLOGICAL EFFECTS
RESPIRATORY SYSTEM
SEROTONIN
LUNG CLEARANCE
CARBON 14 COMPOUNDS
EXCRETION
IN VIVO
RATS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CLEARANCE
DISTRIBUTION
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RODENTS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
560172* - Radiation Effects- Nuclide Kinetics & Toxicology- Animals- (-1987)
550501 - Metabolism- Tracer Techniques