LY79771: A novel compound for weight control

Shaw, Wayne; Schmiegel, Klaus K.; Yen, Terence T.; Toomey, Richard E.; Meyers, Donald B.; Mills, Jack

doi:10.1016/0024-3205(81)90666-4

Cited by 16 publications

(11 citation statements)

References 5 publications

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“…LY226936 decreased food consumption of obese rats as we have shown here. The thennogenic agents we studied (22,33) increased food consumption. Yet both substances decreased body weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…LY226936 did not alter body temperature. Certain thermogenic agents have been shown to increase rectal temperature and the BMR (22). Thermogenic agents are known to normalize glucose intolerance (3,27).…”

Section: Discussionmentioning

confidence: 99%

“…Phenylpiperidine opioid antagonists suppress the appetite of genetically obese Zucker rats (23,24) and phenethanolamine derivatives affect cellular metabolism in such a manner as to prevent the accumulation of body fat in animal models for obesity (1,15,22,27,33). The phenethanolamine compounds are called thermogenic agents because of their mode of action.…”

Section: Introductionmentioning

confidence: 99%

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LY226936 Administered Orally and Centrally to Obese Zucker Rats Suppresses Food Intake and Body Weight Gain

1994

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LY226936, methylcarbamothoic acid-S-(4,5-dihydro-2-thiazolyl) ester, is a new compound that, when administered to obese Zucker rats, caused reduced food intake. LY226936 reduced the food consumption after a single oral dose of 50 and 100 mg/kg. On chronic oral administration to meal-fed obese (5 to 35 mg/kg. once daily) and to fed obese and lean (15 mg/kg. twice daily) Zucker rats, LY226936 reduced food intake and body weight gain for periods ranging from 40 to 48 days. The effect on both parameters was statistically significant. There is no evidence in our studies that tolerance to the actions of LY226936 developed. LY226936 decreased the consumption of both high carbohydrate and high fat diets. Food consumption of meal-fed obese Zucker rats was reduced significantly each time a single dose of 10 ugm LY226936 per rat was infused intracerebroventricularly. None of the receptors studied (mu and kappa opioid, CCK, serotonin, neuropeptide Y, galinin, N-methyl-D-aspartic acid) appeared to bind LY226936 and therefore, appear not to be involved in the depression of food intake by the obese Zucker rat.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LY226936 Administered Orally and Centrally to Obese Zucker Rats Suppresses Food Intake and Body Weight Gain

1994

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“…Essentially, the compounds reduced the fat content of obese animals and affectedtheir body weight (3 -5, 12,28,30,34,40,42,48,52,54,55). In most obese animalmodels, body weight plateaued from the time of administration.…”

Section: Preclinicalmentioning

confidence: 99%

“…In all treated animals, body weight and body fat composition were not totally normalized. A week or two after the initiation of treatment, overeating to maintain a new energy equilibrium, with no concomitant weight gain, was sometimes observed (42,52).…”

Section: Preclinicalmentioning

confidence: 99%

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

Yen

1995

Obesity Research

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YEN,TERENCE T. P-agonists as antiobesity, antidiabetic and nutrient partitioning agents. Obes Res. 1995;3(SupplIn the past decade, the antiobesity, antidiabetic andnutrient partitioning activities of P-agonists have been extensively studied. Thedata generatedfromthesecompounds inexperimentalandfarmanimals haveconvincingly provedthat body fat content andbodyweightcan bemoditiedto somedegreeby a metabolic agent without decreasing food consumption. Marginal antiobesity and antidiabetic activities in humans have been demonstratedwith afew mixed P-agonists under certain conditions, but their utility is limited by side effects. The concept of a P,-receptor rose from the study of these compounds and has beenverified by the cloning and expression of this receptor from several species. Rat p,-selective agonistshaveso far shownno antiobesityefficacyinhumans. The resolution of several issues is critical for the discovery and development of efficacious antiobesity and antidiabetic agents with minimum side effects. Ultimately, the further investigationof these P-agonists and P-receptors shouldlead to a better understanding of the relationship between energy metabolism and feeding behavior.4):5318-5368.

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Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

Yen

1994

Obesity Research

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In several species of obese animals, a group of phenethanolamine beta-agonists stimulates lipolysis and thermogenesis, resulting in the loss of body fat and weight. Brown adipose tissue is considered to be the major target tissue for the antiobesity activity of these compounds. Independent of this antiobesity activity, some of these compounds are also antidiabetic and increase muscle mass. Based on the pharmacological profile of these compounds, a beta3-receptor was proposed and characterized in mouse, rat, and humans. The beta3-receptor in brown adipose tissue has been suggested to mediate the antiobesity activity of these beta-agonists. Whether this receptor is responsible for the antidiabetic activity and whether there is a linkage between the antiobesity/antidiabetic activity and the nutrient partitioning activity is not clear. Clinical trials with these mixed beta-agonists showed marginal antiobesity effects when caloric intake of subjects was restricted. Insulin sensitivity was also improved in some of the trials designed to test the antidiabetic activity of these compounds. Side effects included tachycardia and tremor. To eliminate these side effects, a second generation of compounds was selected for its agonist activity on rat beta3-receptors. Clinical trials with these compounds have shown little increase of energy expenditure even at high doses. Successful development of an antiobesity and antidiabetic drug from this class of compounds will require the elucidation of the physiological role of the human beta3-receptor and the regulatory mechanism between fuel efficiency and feeding behavior.

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LY79771: A novel compound for weight control

Cited by 16 publications

References 5 publications

LY226936 Administered Orally and Centrally to Obese Zucker Rats Suppresses Food Intake and Body Weight Gain

LY226936 Administered Orally and Centrally to Obese Zucker Rats Suppresses Food Intake and Body Weight Gain

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

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