Related Experiment Video
Updated: Aug 6, 2026
09:15
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Cholesterol lowering bile acid binding agents: novel lipophilic polyamines
E W Thomas1, M M Cudahy, C H Spilman
1Upjohn Company, Kalamazoo, Michigan 49001.
Journal of Medicinal Chemistry
|April 3, 1992
Summary
Researchers synthesized novel lipophilic polyamines to lower cholesterol. Two compounds demonstrated significantly higher potency than colestipol hydrochloride in animal studies, offering potential new cholesterol-lowering agents.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Organic Synthesis
Background:
- Hyperlipidemia is a major risk factor for cardiovascular diseases.
- Current lipid-lowering therapies have limitations and side effects.
- Novel therapeutic agents are needed to manage cholesterol levels effectively.
Purpose of the Study:
- To synthesize and characterize novel lipophilic polyamines.
- To evaluate the efficacy of these compounds in lowering animal serum cholesterol levels.
- To compare their potency against a known cholesterol-lowering drug, colestipol hydrochloride.
Main Methods:
- Reductive amination using sodium cyanoborohydride.
- Synthesis of polyamines from ketones, aldehydes, and tris(2-aminoethyl)amine.
- In vivo testing of cholesterol-lowering effects in animal models.
Main Results:
- A series of novel lipophilic polyamines were successfully synthesized.
- Two compounds, N,N-bis[2-(cyclododecylamino)ethyl]-N'-benzyl-1,2-ethanediamine trihydrochloride (36.3HCl) and N,N-bis[2-(cyclododecylmethylamino)ethyl]-N',N'-dimethyl-1,2-ethanediamine (23), were identified.
- Compound 36.3HCl showed 29 times, and compound 23 showed 24 times greater potency than colestipol hydrochloride in reducing animal serum cholesterol.
Conclusions:
- The synthesized lipophilic polyamines represent a promising class of compounds for cholesterol management.
- Compounds 36.3HCl and 23 exhibit superior efficacy compared to colestipol hydrochloride.
- Further research into these novel polyamines could lead to new treatments for hyperlipidemia.
Related Concept Videos
01:31Direct-Acting Cholinergic Agonists: Pharmacokinetics
Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:24Cholinergic Antagonists: Pharmacokinetics
Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and the conjunctiva.
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
01:27Bioavailability Enhancement: Drug Permeability Enhancement
After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...