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 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].

Absorption, Distribution and Excretion
Limaprost reaches peak plasma concentration in about 30 minutes.
Mean total clearance is 1.77 liters per hour.

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Biological Half-Life
The mean half life of elimination is 1.64 hours.

[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 (as Limaprost alfadex; CAS number 88852-12-4) is an oral prostaglandin E1 analog. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostaglandins have a wide variety of actions, including, but not limited to muscular constriction and mediation of inflammation. Limaprost alfadex has been shown to improve peripheral circulatory failure with a vasodilator action and an antithrombotic effect. It also improves poor blood flow in the nerve tissue in cervical spondylosis and normalizes nerve function. Limaprost alfadex was discovered from collaborative research between Ono Pharmaceutical (Ono) and Dainippon Sumitomo Pharma (DSP). It was approved for the treatment of ischemic symptoms such as skin ulcer, pain and coldness accompanying thromboangiitis obliterans in 1988; and for the treatment of subjective symptoms such as pain and numbness in the lower leg and walking disability associated with acquired lumbar spinal canal stenosis as an additional indication in 2001. The drug has been sold under the trade name of Opalmon® Tablets by Ono and Prorenal® Tablets by DSP. In 2011, Ono and DSP initiated Phase II clinical trials in Japan for the treatment of carpal tunnel syndrome. In 2013, these trials were discontinued because the study failed to demonstrate efficacy. Ono and DSP also discontinued the development of limaprost alfadex for the additional indication of cervical spondylosis in 2008 due to the failure to demonstrate the anticipated efficacy in a Phase II study in patients with the disease. However, it was verified by Seoul National University Hospital in November of 2014 that the study on the efficacy of oral limaprost alfadex after surgery for cervical myelopathy was still ongoing.

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Drug Indication
Limaprost is used for the improvement of various ischemic symptoms such as ulcer, pain and feeling of coldness associated with thromboangiitis obliterans as well as improvement of subjective symptoms (pain and numbness of lower legs) and gait ability associated with acquired lumbar spinal canal stenosis (in patients with bilateral intermittent claudication showing normal SLR test result).
FDA Label

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Mechanism of Action
As a prostglandin E1 analog, limaprost acts as an agonist at prostraglandin E2 receptors. It likely stimulates the adenylate cyclase coupled E2 subtype of these receptors to produce smooth muscle relaxation.

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Pharmacodynamics
Limaprost produces vasodilation to improve blood flow to the extremities and increase cutaneous temperature.

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.

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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.

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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.

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