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, maximum plasma concentrations are achieved 1.2 hours after oral dosing.
No pharmacokinetic data available.
No pharmacokinetic data available.
No pharmacokinetic data available.

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Metabolism / Metabolites
No pharmacokinetic data available.

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Biological Half-Life
The half-life is 2.3 hours following oral dosing.

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-phenyl-1-cyclopentanecarboxylic acid 2-[2-(diethylamino)ethoxy]ethyl ester is a member of benzenes.
Pentoxyverine, also referred to as carbetapentane, is a non-opioid central acting antitussive with antimuscarinic, anticonvulsant, and local anesthetic properties. It is an active ingredient in over-the-counter cough suppressants in combination with guaifenesin and H1-receptor antagonists. Pentoxyverine acts on sigma-1 receptors, as well as kappa and mu-opioid receptors. The FDA withdrew the use of all oral gel drug products containing pentoxyverine citrate. Other forms of pentoxyverine citrate continue to be marketed.

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Drug Indication
Indicated as a cough suppressant to relieve cough caused by the common cold, flu, bronchitis, and sinusitis.

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Mechanism of Action
While the mechanism of antitussive action of pentoxyverine is not fully understood, it is thought to be mediated via sigma-1 receptors expressed in the central nervous system. Pentoxyverine acts as an agonist at sigma receptors with the Ki of 75±28 nM, as demonstrated in a competitive binding assay. The function of sigma receptors on cough suppressant activities is unclear, however these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem where the afferent fibres first synapse. NTS is located very close to the cough centre in the brainstem thus may function as a ‘gate' for the cough reflex and allow sigma-1 receptor agonists to modulate afferent activity prior to reaching the cough center. It is suggested that highly lipophilic sigma-1 agonists may penetrate the CNS following systemic administration. When administered as aerosols, sigma-1 receptor agonists may temporarily act in the periphery to modulate cough by acting activate sigma receptors expressed in the lungs. However there is limited evidence of peripheral localization of the sigma agonists following aerosol administration and the ruling out of systemic exposure. The local anesthesia action of pentoxyverine may occur through inhibition of voltage-gated Na(+) currents.
NUMBER OF DRUGS ARE KNOWN TO REDUCE COUGH AS RESULT OF THEIR CENTRAL ACTIONS, ALTHOUGH EXACT MECHANISMS ARE STILL NOT ENTIRELY CLEAR. /NONOPIOID ANTITUSSIVES/

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Therapeutic Uses
Antitussive Agents
...DRUGS THAT HAVE BEEN USED AS CENTRALLY ACTING ANTITUSSIVES INCL...CARBETAPENTANE...

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Drug Warnings
OTHER DRUGS THAT HAVE BEEN USED AS...ANTITUSSIVES INCL...CARBETAPENTANE, CARAMIPHEN, & OXOLAMINE. ...IN GENERAL THEIR TOXICITY IS LOW, BUT CONTROLLED CLINICAL STUDIES ARE STILL INSUFFICIENT TO DETERMINE WHETHER THEY MERIT CONSIDERATION AS ALTERNATIVES TO MORE THOROUGHLY STUDIED AGENTS.
GENERALLY, ANY CENTRALLY ACTING ANTITUSSIVE SHOULD BE GIVEN CAUTIOUSLY WITH OTHER CENTRALLY ACTING AGENTS. /ANTITUSSIVES/

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Pharmacodynamics
Pentoxyverine induces an antitussive action. In animal studies, intraperitoneal administration of pentoxyverine inhibited citric-acid-induced cough in guinea-pigs _in vivo_. Some mice and rat studies suggest that pentoxyverine may also exert anticonvulsant activities without inducing a protective effect from NMDA-induced lethality. Protective effects against maximal electroshock-induced seizures in a dose-related fashion was also observed following either intraperitoneal or oral administration. In hERG-transfected cells, pentoxyverine inhibited the outward current of the hERG ion channel with half-maximal inhibition concentrations (IC50) of 3.0 µM. In rats receiving intrathecal administration, pentoxyverine exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade. It induced a spinal blockade with a more sensory/nociceptive-selective action over motor blockade compared to lidocaine.

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.)