Limaprost is an analogue of alprostadil (prostaglandin E1). Its primary mechanisms of action are vasodilation, increasing blood flow, and inhibition of platelet aggregation. [2]

In human IVD cells, limaprost has an IC50 value of 70.9 nM and inhibits IL-1-mediated nerve growth factor (NGF) induction in a concentration-dependent manner [3].

---

In an in vitro study using guinea-pig platelets, the inhibitory effect of limaprost on platelet aggregation and platelet adhesiveness was 10- to 16-fold and 20-fold more potent than that of epoprostenol (prostacyclin). [2]
In an in vitro study with human platelets, limaprost inhibited platelet aggregation with similar potency to that of epoprostenol. [2]
In an in vitro study, limaprost was highly protein bound in human plasma (95.8%). [2]

In rats, the vasopressin-induced ECG ST depression is alleviated when limaprost (OP1206) is administered orally at doses greater than 100 μg/kg [1]. Myocardial oxygen consumption, redox potential, heart rate, blood pressure, and myocardial blood flow are all unaffected by intracoronary injection of limaprost (OP1206; 1-100 ng/kg) in dogs [1]. Dogs' resistance in their big and small coronary arteries is decreased when limaprost (OP1206; 1-3 mg/kg) is injected intravenously [1]. When administered to guinea pigs at doses equivalent to or less than those that alleviate vasopressin-induced electrocardiographic ST depression, oral limaprost (OP1206) decreases platelet aggregation, adhesion, bleeding time, and thrombocytopenia caused by ADP and collagen infusion. Manifestations [1].

---

In an animal model of peripheral circulatory disorder, oral administration of limaprost inhibited the development of ischemic lesions in limbs and peripheral extremities. [2]
In an in vivo guinea-pig model of electrically induced thrombosis, limaprost significantly (p<0.05) inhibited thrombus formation. [2]
In animal models relevant to Lumbar Spinal Canal Stenosis (LSCS), limaprost improved blood flow to the cauda equina, sciatic nerve, and nerve tissue in the lumbar vertebral canal. It also increased the diameter of the cauda equina blood capillary. [2]
In animal models of LSCS, intravenous limaprost inhibited an induced reduction in nerve conduction velocity in the cauda equina nerve. Oral administration inhibited the prolongation of heat-stimulated myogenic nerve discharges in rat femoral muscles caused by sciatic nerve ligation and reduced hyperalgesia in another rat model of disturbed sciatic nerve function. [2]
In in vivo rat models of walking dysfunction, oral administration of limaprost significantly (p<0.05) increased walking or running distance compared with a sham control. [2]

In an animal model of peripheral circulatory disorder (species not specified), oral administration of limaprost was used to assess its effect on inhibiting ischemic lesions in limbs. [2]
In an in vivo guinea-pig model of electrically induced thrombosis, limaprost was administered to evaluate its inhibitory effect on thrombus formation, assessed by the change in the threshold voltage for thrombus formation. [2]
In dog models, limaprost decreased coronary vessel resistance, increased coronary blood flow, and increased femoral arterial and cutaneous blood flow in hind limbs. [2]
In animal models of LSCS, the effects of limaprost on blood flow in the cauda equina and sciatic nerve were studied. Blood flow in tissue between ligations around the right sciatic nerve and in the nerve tissue of the fifth lumbar vertebra was measured after multiple-dose oral administration of limaprost. [2]
In a rat model, intravenous limaprost was administered to assess its effect on nerve conduction velocity in the cauda equina nerve. [2]
In rat models of sciatic nerve dysfunction, oral limaprost was administered chronically to evaluate its effect on hyperalgesia and on heat-stimulated myogenic nerve discharges. [2]
In rat models of walking dysfunction, oral limaprost was administered to measure its impact on walking or running distance. [2]

Absorption, Distribution and Excretion
Limaprost reaches peak plasma concentration in about 30 minutes. The mean total clearance is 1.77 L/h. Biological Half-Life The mean elimination half-life is 1.64 h. Limaprost is rapidly absorbed after oral administration. In healthy volunteers, the median time to peak plasma concentration (t_max) after a single 5 μg dose was 0.75 h, and after a 10 μg dose was 0.5 h. [2] The mean maximum plasma concentration (C_max) after a single 5 μg dose was 1.18 pg/mL, and after a 10 μg dose was 2.06 pg/mL. The mean area under the concentration-time curve (AUC_∞) for the 5 μg and 10 μg dose groups were 1.97 pg•h/mL and 3.43 pg•h/mL, respectively. [2]
Absorption appears to be dose-dependent within the tested range. [2]
Limaprost has a high protein binding rate (95.8%) in human plasma. [2]
The mean elimination half-life is approximately 1 hour after a single oral dose of 5 μg or 10 μg. [2]
In a rat study, approximately 70% of the radiolabeled dose was excreted in feces within 96 hours and 30% in urine. Two major metabolites were identified, primarily excreted in feces and bile. The extent/site of metabolism and excretion pathway in humans have not been investigated. [2]

In clinical trials of TAO and LSCS, oral administration of 3–30 μg limaprost was generally well tolerated. The most common treatment-related adverse events included gastrointestinal reactions (e.g., diarrhea, nausea, abdominal discomfort), rash, hot flashes/flushing, headache, and anemia. [2] In TAO patients (pooled analysis, n=4582), reported adverse events included diarrhea (1.1%), nausea/vomiting/regurgitation (0.5%), hot flashes/flushing (0.5%), rash (0.4%), and abdominal/upper abdominal discomfort (0.4%). In LSCS patients (pooled analysis, n=397), 25 gastrointestinal-related adverse events were recorded. [2] Other adverse events occurring in 0.2% to 0.3% of TAO patients included abdominal pain/stomach pain, headache, abnormal liver function (e.g., elevated AST/ALT), and anorexia. [2]
In one trial, three patients treated with a dose of 30 μg/day reported serious adverse events leading to discontinuation of the drug (gastrointestinal-related events and elevated AST/ALT). [2]
A small number of patients experienced thrombocytopenia, elevated blood urea nitrogen, liver dysfunction, or jaundice. [2]
Pharmacodynamic interactions (increased bleeding tendency) may occur if used in combination with antiplatelet drugs (e.g., aspirin, ticlopidine), thrombolytic drugs (e.g., urokinase), or anticoagulants (e.g., heparin, warfarin). [2]

[1]. Pharmacological evaluation of OP 1206, a prostaglandin E1 derivative, as an antianginal agent. Arch Int Pharmacodyn Ther. 1980 Sep;247(1):89-102.

[2]. Limaprost. Drugs. 2007;67(1):109-18; discussion 119-20.

[3]. PGE1 Attenuates IL-1β-induced NGF Expression in Human Intervertebral Disc Cells. Spine (Phila Pa 1976). 2016 Jun;41(12):E710-6.

Limaprost is a long-chain fatty acid. Limaprost (trade name: Limaprost alfadexamethasone; CAS No.: 88852-12-4) is an oral prostaglandin E1 analog. Prostaglandins act on various cells, such as vascular smooth muscle cells, causing vasoconstriction or vasodilation; platelets, causing platelet aggregation or disaggregation; and spinal cord neurons, causing pain. Prostaglandins have a wide range of effects, including but not limited to muscle contraction and inflammation regulation. Limaprost alfadexamethasone has been shown to improve peripheral circulatory failure through vasodilatory and antithrombotic effects. It can also improve poor blood perfusion in cervical spondylosis nerve tissue and restore normal nerve function. Limaprost alfadexamethasone is the result of collaborative research between Ono Pharmaceutical Co., Ltd. (Ono) and Sumitomo Pharmaceutical Co., Ltd. (DSP). This drug was approved in 1988 for the treatment of ischemic symptoms caused by thromboangiitis obliterans, such as skin ulcers, pain, and coldness; and in 2001 for the treatment of subjective symptoms such as lower limb pain, numbness, and gait disturbances caused by acquired lumbar spinal stenosis. It is marketed by Ono Pharmaceutical Co., Ltd. under the brand name Opalmon® tablets, and by DSP Pharmaceuticals under the brand name Prorenal® tablets. In 2011, Ono Pharmaceutical Co., Ltd. and DSP Pharmaceuticals initiated a Phase II clinical trial in Japan for lima prostol in the treatment of carpal tunnel syndrome. In 2013, the trial was terminated because the study failed to demonstrate efficacy. Furthermore, due to the failure to demonstrate the expected efficacy in a Phase II study of patients with cervical spondylosis, Ono Pharmaceutical Co., Ltd. and DSP Pharmaceuticals terminated their Phase II clinical trial of lima prostol and alfadexamethasone for the treatment of cervical spondylosis in 2008. However, Seoul National University Hospital confirmed in November 2014 that research on the efficacy of oral limaprost-alfadexamethasone in treating cervical spondylosis after surgery is still ongoing. Drug Indications: Limaprost is used to improve various ischemic symptoms associated with thromboangiitis obliterans, such as ulceration, pain, and coldness, as well as to improve subjective symptoms (lower extremity pain and numbness) and gait ability associated with acquired lumbar spinal stenosis (for patients with bilateral intermittent claudication and normal straight leg raise test results). FDA Label: Mechanism of Action: As a prostaglandin E1 analog, limaprost acts as an agonist of prostaglandin E2 receptors. It may stimulate the adenylate cyclase-coupled E2 isoform of these receptors, thereby producing smooth muscle relaxation. Pharmacodynamics: Limaprost causes vasodilation, improves blood flow to the extremities, and increases skin temperature.

---

Limaprost (Opalmon®) is an oral active prostaglandin E1 analog developed in Japan. [2]
It is approved in Japan for two indications: 1) for the treatment of ischemic symptoms (ulceration, coldness, pain) in adult patients with thromboangiitis obliterans (TAO/Burgh's disease); 2) for the treatment of pain, numbness, and gait abnormalities in adult patients with acquired lumbar spinal stenosis (LSCS) who have bilateral intermittent claudication and normal straight leg raise test results. [2]
For thromboangiitis obliterans (TAO), the recommended daily oral dose is 30 μg (divided into three doses); for lumbar spinal stenosis (LSCS), the recommended daily oral dose is 15 μg (divided into three doses). [2]
In a 6-week randomized, double-blind trial of lima prostol daily in 136 Japanese patients with TAO, 30 μg of lima prostol daily showed no significant difference in efficacy compared to 500 μg of oral ticlopidine daily in improving ischemic symptoms. [2]
In a phase III trial of 146 patients with LSCS, 15 μg of lima prostol daily was superior to 3 μg daily in terms of overall drug efficacy and overall improvement. In a phase II trial, 15 μg daily was not significantly different from 30 μg daily, but was superior to 6 μg daily, thus establishing 15 μg daily as the optimal dose for LSCS. [2]
Post-marketing surveillance of cesarean section patients (n=1800) treated with lima prostol showed an overall improvement rate of 49.9%. Walking ability was significantly improved, with the proportion of patients unable to walk 500 meters after treatment decreasing from 55.7% to 27.4%. [2]

C22H36O5

380.51800

380.256

74397-12-9

Limaprost-d3;1263190-37-9

6438378

White to off-white solid powder

1.1±0.1 g/cm3

550.6±50.0 °C at 760 mmHg

97-100°

300.9±26.6 °C

0.0±3.4 mmHg at 25°C

1.551

3.15

3

5

13

27

511

5

CCCC[C@H](C)C[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1CCCC/C=C/C(=O)O)O)O

OJZYRQPMEIEQFC-UAWLTFRCSA-N

InChI=1S/C22H36O5/c1-3-4-9-16(2)14-17(23)12-13-19-18(20(24)15-21(19)25)10-7-5-6-8-11-22(26)27/h8,11-13,16-19,21,23,25H,3-7,9-10,14-15H2,1-2H3,(H,26,27)/b11-8+,13-12+/t16-,17+,18+,19+,21+/m0/s1

(2E,11-alpha,13E,15S,17S)-11,15-Dihydroxy-17,20-dimethyl-9-oxoprosta-2,13-dien-1-oic acid

ONO 1206; OP1206; ONO 1206; ONO 1206; OP 1206; Limaprost; 17α,20-dimethyl-Δ2-Prostaglandin E1; 17α,20-dimethyl-δ2-PGE1; OP-1206

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 : ≥ 40 mg/mL (~105.12 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.47 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 20.8 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: ≥ 2.08 mg/mL (5.47 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 20.8 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: ≥ 2.08 mg/mL (5.47 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 20.8 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.)