Chlorpropamide targets the sulfonylurea receptor (SUR) on pancreatic β-cells, which is an ATP-sensitive potassium channel (K_ATP). Binding to this receptor inhibits potassium efflux, depolarizing the cell membrane. This opens voltage-gated calcium channels, increasing intracellular calcium, which stimulates insulin secretion from pancreatic β-cells.

In vitro, chlorpropamide stimulates insulin release from isolated pancreatic islets or β-cell lines. It binds to the sulfonylurea receptor with high affinity. Specific IC₅₀ values for receptor binding and insulin secretion are documented in the literature but not detailed in the available results.

In vivo, chlorpropamide lowers blood glucose levels in patients with type 2 diabetes mellitus by stimulating insulin secretion. It is used as monotherapy as an adjunct to diet and exercise. It has a long duration of action (up to 24 hours) allowing for once-daily dosing. It is effective in patients with residual pancreatic β-cell function.

Sulfonylurea receptor binding assays are performed using membrane preparations from pancreatic β-cells or insulinoma cell lines. Radioligand binding studies use [³H]-glibenclamide or [³H]-glyburide to assess competitive displacement by chlorpropamide. IC₅₀/Ki values are calculated from competition binding curves.

Insulin-secreting cell lines (e.g., MIN6, INS-1) or isolated pancreatic islets are used. Cells are treated with chlorpropamide at various concentrations in glucose-containing media. Insulin secretion is measured by ELISA or RIA. Intracellular calcium is measured using fluorescent indicators (e.g., Fura-2). K_ATP channel activity is assessed by patch-clamp electrophysiology.

In vivo efficacy is evaluated in animal models of diabetes (e.g., streptozotocin-induced diabetic rats, db/db mice) and in human clinical trials. Chlorpropamide is administered orally, and blood glucose and insulin levels are measured. Oral glucose tolerance tests (OGTT) are performed to assess glycemic control. Long-term efficacy is evaluated by HbA1c levels.

Absorption, Distribution and Excretion
Frequently absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 2–4 hours, with an onset of action of 1 hour. Maximum efficacy is achieved 3–6 hours after oral administration of chlorpropamide. 80–90% of a single oral dose is excreted unchanged in the urine within 96 hours as metabolites. …Frequently absorbed from the gastrointestinal tract… Excretion (percentage)…60 /from table/ …20% excreted unchanged;… /from table/ Frequently absorbed from the gastrointestinal tract after oral administration of chlorpropamide. The drug is detectable in plasma within 1 hour after a single oral dose, with peak plasma chlorpropamide concentrations occurring within 2–4 hours. For more complete data on the absorption, distribution, and excretion of chlorpropamides (6 in total), please visit the HSDB record page.

---

Metabolism/Metabolites
Up to 80% of the dose may be metabolized in the liver to 2-hydroxychloropropionamide (2-OH CPA), p-chlorobenzenesulfonylurea (CBSU), 3-hydroxychloropropionamide (3-OH CPA), and p-chlorobenzenesulfonamide (CBSA); CBSA may be produced through urinary breakdown. Whether chloropropionamide metabolites have a hypoglycemic effect is unknown.
...Chloropropionamide is not completely metabolized; approximately 20% of the drug is excreted unchanged.
...Partial hydrolysis of urea has been detected, generating sulfonamide derivatives...Recent evidence suggests...this may be an artificial product, not a true metabolite...
In one subject, after oral administration of tritium-labeled chloropropionamide...80% of the dose was excreted within 7 days. The metabolite...is p-chlorobenzenesulfonamide...[(p-chlorophenyl)sulfonyl]urea...1-[(p-chlorophenyl)sulfonyl]-3-(2-hydroxypropyl)urea. ...&.1-[(p-chlorophenyl)sulfonyl]-3-(3-hydroxypropyl)urea...
...For diabetic patients.../chloropropionamide/...dosage is...250-500 mg...excretion products...include.../(p-chlorophenyl)sulfonylurea/ (21%).../p-chlorobenzenesulfonamide/ (2%), 2-hydroxychloropropionamide (55%) and 3-hydroxychloropropionamide (2%).
For more complete data on the metabolism/metabolites of chloropropionamide (6 in total), please visit the HSDB record page.
Known human metabolites of chloropropionamide include p-chlorobenzenesulfonylurea, 2-hydroxychloropropionamide and 3-hydroxychloropropionamide.

---

Biological half-life
Approximately 36 hours, with significant individual variability, ranging from 25-60 hours. Duration of action is at least 24 hours.
Chloropropionamide has a longer half-life (24 to 48 hours). Half-life...24-48 hours / (Data from table)
Chlorpropamide is well-absorbed orally with high bioavailability. It has a long half-life (~36 hours) allowing for once-daily dosing. It is metabolized in the liver and excreted in urine. Its long duration of action increases the risk of hypoglycemia. Protein binding is high (~90%).

Effects During Pregnancy and Lactation
◉ Summary of Use During Lactation
Chlorpropamide has been discontinued in the United States. Limited data suggest that chlorpropamide levels in breast milk are unlikely to affect breastfed infants. To avoid drug accumulation, short-acting medications are generally recommended during lactation. Breastfed infants should be monitored for signs of hypoglycemia, such as irritability, lethargy, feeding difficulties, seizures, cyanosis, apnea, or hypothermia. If there is any concern, monitoring of the breastfed infant's blood glucose levels is recommended while the mother is on hypoglycemic medication.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

---

Protein Binding
Highly bound to plasma proteins.

---

Interactions
Medications that may increase the risk of hypoglycemia… include other hypoglycemic agents, sulfonamides, propranolol, salicylates, phenylbutazone, probenecid, dicumarol, chloramphenicol, monoamine oxidase inhibitors, and alcohol. /Sulfonylureas/
Allopurinol or its metabolites may compete with chlorpropamide for renal tubular secretion, leading to enhanced chlorpropamide efficacy in a small number of patients.
Diphenylam-like reactions may occur when taking any sulfonylurea medication and consuming alcohol concurrently, mainly manifested as facial, neck, and arm flushing… /Sulfonylureas/
The risk of hypoglycemia may increase or its duration may be prolonged when taking sulfonylureas and consuming moderate to large amounts of alcohol concurrently; small amounts of alcohol (after meals) usually do not cause hypoglycemia. /Sulfonylureas/
For more complete data on interactions of chlorpropamides (19 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rats oral LD50: 2390 mg/kg
Rats intravenous LD50: 590 mg/kg
Dogs intravenous LD50: 575 mg/kg
Dogs oral LD50: 800 mg/kg
Mouse oral LD50: 1680 mg/kg

Chlorpropamide is generally well-tolerated, but hypoglycemia is the most significant adverse effect, especially in elderly patients or those with renal impairment. Other adverse effects include weight gain, gastrointestinal disturbances, and rare hematological reactions. It has drug interactions with sulfonamides, NSAIDs, and other protein-bound drugs.

Therapeutic Uses
Hypoglycemic Agents: Sulfonylureas are used to control hyperglycemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) whose blood sugar cannot be effectively controlled by dietary adjustments alone. /Sulfonylureas/ …Effective in adult-onset diabetes patients whose pancreas still has the ability to secrete insulin. /Sulfonylureas/ Veterinary Use: Used to treat canine diabetes.
For more complete therapeutic use data on chlorpromazine (8 types), please visit the HSDB record page.

---

Drug Warnings …Studies…indicate…an increased incidence of difficulties in patients taking oral hypoglycemic agents. Ventricular tachycardia and ventricular fibrillation often occur in the early stages of myocardial infarction. Sulfonylureas: Sulfonylureas should be used with caution in patients with renal or hepatic impairment. Veterinarian: Avoid use in pregnant animals. Veterinarian: Sulfonylureas are of very limited efficacy in the treatment of canine diabetes, with only a very small number of mild cases showing improvement. /Sulfonylureas for Lowering Blood Glucose/
For more complete data on chlorpromazine (18 in total), please visit the HSDB records page.

---

Pharmacodynamics
Chlorpromazine is a second-generation sulfonylurea used in combination with diet therapy to lower blood glucose levels in patients with type 2 diabetes. Chlorpromazine is twice as potent as glipizide, another second-generation sulfonylurea.
Chlorpropamide is a sulfonylurea antidiabetic agent used for the treatment of type 2 diabetes. It was one of the first oral hypoglycemic agents introduced for clinical use. Its use has declined with the availability of newer sulfonylureas (e.g., glipizide, glyburide) and other antidiabetic agents (e.g., metformin, DPP-4 inhibitors) due to its long half-life and higher risk of hypoglycemia. It is still available in some countries.

C10H13CLN2O3S

276.74

276.033

94-20-2

2727

White to off-white solid powder

1.4±0.1 g/cm3

433.5±47.0 °C at 760 mmHg

128 °C

216.0±29.3 °C

0.0±1.1 mmHg at 25°C

1.585

2.8

2

3

4

17

345

0

RKWGIWYCVPQPMF-UHFFFAOYSA-N

InChI=1S/C10H13ClN2O3S/c1-2-7-12-10(14)13-17(15,16)9-5-3-8(11)4-6-9/h3-6H,2,7H2,1H3,(H2,12,13,14)

1-(4-chlorophenyl)sulfonyl-3-propylurea

Diabinese; Chloropropamide; Chlorpropamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~361.35 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)