At a Ki of 75 nM, pentovirine binds to the [3H]-pentazocine tagged location on the meninges of guinea pigs in a competitive manner [4].

In guinea pigs, pentovirine (1–5 mg/kg; single intraperitoneal injection) reduces coughing caused by citric acid [4].

Absorption, Distribution and Excretion
In humans, peak plasma concentrations are reached 1.2 hours after oral administration. Pharmacokinetic Data Unavailable Pharmacokinetic Data Unavailable Pharmacokinetic Data Unavailable Metabolism/Metabolites Pharmacokinetic Data Unavailable Biological Half-Life The half-life after oral administration is 2.3 hours.

Protein Binding

No pharmacokinetic data available.

[1]. Novel 1-phenylcycloalkanecarboxylic acid derivatives are potent and selective sigma 1 ligands. J Med Chem. 1994 Jul 22;37(15):2285-91.

[2]. Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004 Jan;141(2):233-40.

[3]. Extraction-free spectrophotometric assay of the antitussive drug pentoxyverine citrate using sulfonephthalein dyes. Spectrochim Acta A Mol Biomol Spectrosc. 2019 Nov 5;222:117186.

[4]. Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the Nociceptive System with Capsaicin. Sci Rep. 2016 Nov 25:6:37835. doi: 10.1038/srep37835.

[5]. In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves. Evid Based Complement Alternat Med. 2015:2015:428208.

1-Phenylacetic acid 2-[2-(diethylamino)ethoxy]ethyl ester belongs to the benzene family of compounds.
Pethylverine (also known as carbetapentane) is a non-opioid centrally acting antitussive with antimuscarinic, anticonvulsant, and local anesthetic effects. It is used in combination with guaifenesin and H1 receptor antagonists and is the active ingredient in many over-the-counter cough medicines. Pethylverine acts on σ-1 receptors as well as κ and μ opioid receptors. The U.S. Food and Drug Administration (FDA) has revoked the approval of all oral gel formulations containing pethylverine citrate. Other forms of pethylverine citrate are still available on the market.
Indications
For the relief of cough caused by the common cold, influenza, bronchitis, and sinusitis.
Mechanism of Action
The mechanism of action of pethylverine's antitussive effect is not fully understood, but it is generally believed to be mediated by σ-1 receptors expressed in the central nervous system. Pentovirine, as a σ receptor agonist, has a Ki value of 75 ± 28 nM, as confirmed in competitive binding assays. The role of σ receptors in antitussive activity is unclear, but these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem, where afferent fibers first form synapses. Located near the brainstem cough center, the NTS may act as a "gateway" for the cough reflex, allowing σ-1 receptor agonists to modulate the cough reflex before afferent nerves reach the cough center. Studies have shown that highly lipophilic σ-1 receptor agonists may penetrate the central nervous system after systemic administration. When administered as an aerosol, σ-1 receptor agonists may act temporarily peripherally, modulating cough by activating σ receptors expressed in the lungs. However, current evidence regarding the peripheral localization of σ receptor agonists after aerosol administration and the exclusion of systemic exposure is limited. The local anesthetic effect of pentoxifylline may be achieved by inhibiting voltage-gated sodium ion currents. Many drugs are known to reduce cough through their central action, but their exact mechanisms remain not fully understood. /Non-Opioid Antitussives/

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Therapeutic Use
Antussis
...Drugs previously used as centrally acting antitussives include...carbeta-spray...

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Drug Warnings
Other drugs previously used as...antitussives include...carbeta-spray, caramifen, and oxoramine. ...Overall, they have low toxicity, but there is currently a lack of sufficient controlled clinical studies to determine whether they are worthwhile alternatives to more well-studied drugs.
Generally, any centrally acting antitussive should be used with caution in combination with other centrally acting antitussives. /Antussis/

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Pharmacodynamics
Pentanone can cause antitussive effects. Animal studies have shown that intraperitoneal injection of pentanone can inhibit citric acid-induced cough in guinea pigs. Some mouse and rat studies have shown that pentanone may also have anticonvulsant activity and does not provide protection against NMDA receptor-induced lethality. Following intraperitoneal or oral administration, penoxyverine demonstrated a dose-dependent protective effect against maximal electroshock-induced seizures. In hERG-transfected cells, penoxyverine inhibited the outward current of hERG ion channels at a half-maximal inhibitory concentration (IC50) of 3.0 µM. In rats receiving intrathecal injection, penoxyverine exhibited a dose-dependent spinal cord blockade effect, with stronger sensory selectivity than motor blockade. Compared to lidocaine, penoxyverine-induced spinal cord blockade showed stronger sensory/nociceptive selectivity than motor blockade.

C20H31NO3

333.46504

333.23

77-23-6

Pentoxyverine citrate;23142-01-0

2562

White to off-white solid powder

1.0±0.1 g/cm3

435.5±30.0 °C at 760 mmHg

90-95

217.2±24.6 °C

0.0±1.0 mmHg at 25°C

1.517

3.29

0

4

11

24

356

0

CFJMRBQWBDQYMK-UHFFFAOYSA-N

InChI=1S/C20H31NO3/c1-3-21(4-2)14-15-23-16-17-24-19(22)20(12-8-9-13-20)18-10-6-5-7-11-18/h5-7,10-11H,3-4,8-9,12-17H2,1-2H3

2-[2-(diethylamino)ethoxy]ethyl 1-phenylcyclopentane-1-carboxylate

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 : ~250 mg/mL (~749.69 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.24 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 (6.24 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 (6.24 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.)