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Biomedical subjects

R E Tessel

Publications and source records attributed to R E Tessel.

45 records · Page 3Linked to original sources
PubMed1975

Fenfluramine and N-ethyl amphetamine: comparison of the reinforcing and rate-decreasing actions in the rhesus monkey.

N-ethyl amphetamine HCl (NEA) and fenfluramine HCl (meta-trifluoromethyl N-ethyl amphetamine) were evaluated as reinforcers in rhesus monkeys that had been previously trained to press a lever using food presentations and cocaine HCl injections as reinforcers. Each daily session consisted of episodic opportunities to obtain reinforcers under a fixed-ratio schedule of 30. A drug period was interpolated between two periods in which lever-press responding was maintained by food presentations. Compared to saline, none of the drugs altered the rate of responding in the food periods which preceded the drug sessions, indicating the absence of residual response-disrupting drug actions from previous sessions. However, NEA and fenfluramine self-injection resulted in dose-related decreases in response rates during the food periods which immediately followed the drug sessions. Cocaine HCl (30 mug/kg/injection) maintained high response rates at over one response/second during the drug periods, as did the same dose of NEA. Doses of 10 and 100 mug/kg/injection of NEA as well as all doses of fenfluramine HCl (10 through 300 mug/kg/injection) maintained rates that were not different from those associated with saline injections. These results substantiate and extend earlier findings with fenfluramine and indicate that its failure to act as a reinforcer is attributable to its meta-trifluoromethyl group.

Amphetamines↗
PubMed1975

Structure-activity relationships between meta-substituted N-ethylamphetamines and locomotor activity in mice.

The effects of N-ethylamphetamines substituted at the meta position of the phenyl ring with H, F, Cl, Br, I, CF3, CH3O, NO2 or OH were examined on locomotor activity in mice. With the exception of meta-CF3-N-ethylamphetamine (fenfluramine), all compounds stimulated locomotor activity to varying amounts as determined in dose-activity curves that included doses which were ineffective through doses which either decreased activity relative to lower doses or were lethal. Multiple linear regression analyses indicated that the extent to which these compounds increased locomotor activity was inversely related to meta-substituent steric effects (size, r equal to 0.90), whereas hydrophobic and electronic substituent effects did not contribute significantly to this relationship. In mice pretreated with pargyline (100 mg/kg, 4 hours), the stimulant effects of these compounds were potentiated and again were inversely related only to substituent size (r equal to 0.77). In reserpine-pretreated mice (5 mg/kg, 24 hours), no relationship was obtained with size, hydrophobic or electronic effects individually or together. Reserpine pretreatment eliminated the rate-increasing effects of the iodinated and hydroxylated derivatives but not those of the other compounds. Pretreatment with alpha-methyl-para-tyrosine (100 or 320 mg/kg, 1 hour) caused a dose-related abolition of N-ethylamphetamine-induced increases in acitivity. These data suggest that the amphetamine derivatives of the present study act indirectly, probably through release of catecholamines.

Amphetamine↗
PubMed1975

Structure-activity relationships between meta-substituted N-ethylamphetamines and isolated guinea-pig atrial rate.

The effects of N-ethylamphetamines (NEAs) substituted at the meta position of the phenyl ring with H, F, Cl, Br, I, CF3, CH3O, NO2, or OH were examined on the rate of spontaneously beating isolated guinea-pig atria. All compounds, with the exception of meta-iodo NEA and meta-trifluoromethyl NEA (fenfluramine), increased atrial rate to varying degrees, as determined in cumulative concentration-response curves that included concentrations which were ineffective through those which decreased rate. Multiple linear regression analyses indicated that the respective maximum increases in atrial rate produced by these compounds were inversely related to the meta-substituted steric factor (size); neither hydrophobic nor electronic substituent effects contributed significantly to the relationship. In atria obtained from guinea pigs pretreated with the monoamine oxidase inhibitor, pargyline (100 mg/kg, 4 hours pretreatment), the stimulant effects of these compounds were markedly potentiated and were again inversely related only to substituent size. In addition, after pargyline, meta-iodo NEA and fenfluramine greatly stimulated the atria. In atria. In atria obtained from guinea pigs which had been administered reserpine (5 mg/kg, 24 hours pretreatment), none of the compounds except meta-hydroxy NEA increased atrial rate. The interactions of pargyline and reserpine pretreatment with the actions of these NEA congeners suggest that all are indirectly acting sympathomimetic amines, except the hydroxylated compound, which is mixed-acting.

Amphetamine↗
PubMed1974

Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey.

Fenfluramine, over a dose range from 0.003 to 3 milligrams per kilogram of body weight, failed to maintain self-injection behavior in rhesus monkeys that had initiated and maintained responding for cocaine or methohexital. This absence of a positive reinforcing effect could not be attributed to a slow onset of drug effect or to the use of behaviorally inactive doses. Fenfluramine, because of its distinctive properties, may produce fewer problems of human abuse than do amphetamine-type agents.

Animals↗
PubMedDate not supplied

Neuropeptide Y and peptide YY neuronal and endocrine systems.

An extensive system of neuropeptide Y (NPY) containing neurons has recently been identified in the central and peripheral nervous system. In addition, NPY and a structurally related peptide, peptide YY (PYY), containing endocrine cells have been identified in the periphery. The NPY system is of particular interest as the peptide coexists with catecholamines in the central and sympathetic nervous system and adrenal medulla. Evidence has been presented which indicates that NPY may play important roles in regulating autonomic function.

Animals↗
PubMedDate not supplied

Amphetamine-induced changes in immunoreactive NPY in rat brain, pineal gland and plasma.

Acute injection of d-amphetamine (10 mg/kg), administered to rats 60 minutes prior to sacrifice, induced a doubling of immunoreactive NPY (NPY-IR) in pineal gland. No changes, however, could be detected in levels of NPY-IR in grossly dissected or microdissected regions of rat brain, nor were changes evident in plasma level concentrations of NPY-IR following acute amphetamine pretreatment. When amphetamine was injected twice daily for six days and once more 60 minutes prior to sacrifice, levels of NPY-IR were decreased in caudate putamen and the paraventricular and dorsomedial nuclei of the hypothalamus, while concentrations of NPY-IR were increased in medial preoptic nucleus, pineal gland, and plasma. These data indicate that levels of NPY-IR are susceptible to manipulation by amphetamine, where the extent and direction of change (increase or decrease) depends on both the frequency of drug administration and the nature of the sampled tissue. Based on the effects of amphetamine on central and peripheral norepinephrine and epinephrine disposition observed in other studies, the data also suggest that NPY-IR and catecholamine dispositions are not directly correlated and may be inversely related in some tissue.

Animals↗