**Background**
The sigma-1 receptor ($\sigma_1$R) is a unique chaperone protein located primarily in the endoplasmic reticulum membrane, playing a critical role in modulating calcium signaling, protein folding, and cellular stress responses. Due to its widespread expression in the central and peripheral nervous systems, $\sigma_1$R has become a significant target for treating various neurological and respiratory disorders. In particular, the modulation of $\sigma_1$R is closely linked to the regulation of the cough reflex and bronchial smooth muscle tone. Agents that target this receptor can provide potent antitussive and spasmolytic effects, making them valuable for managing airway resistance and bronchial interceptions. In this context, we will introduce a potent sigma-1 receptor agonist – Pentoxyverine.
**Definition**
Pentoxyverine (Carbetapentane) citrate is an orally active, blood-brain barrier permeable sigma-1 receptor agonist and muscarinic antagonist. According to the Pentoxyverine technical information, it exhibits $K_i$ values of 41 nM for $\sigma_1$, 894 nM for $\sigma_2$, and 75 nM for guinea-pig brain membrane $\sigma_1$.
**In Vitro and In Vivo Studies**
The Pentoxyverine biological activity is characterized by its ability to act as a potent antitussive, anticonvulsant, and spasmolytic agent. In vivo studies have demonstrated its complex role in nociception and respiratory control. In a model using female wild-type mice (25-30 g), Pentoxyverine (0.5, 1, 2, 4, 8, 16, 32 mg/kg; SC) administered 30 minutes before intraplantar capsaicin (0.125 $\mu$g) dose-dependently potentiated the sensitizing effect of capsaicin to mechanical stimuli. Specifically, a dose of 16 mg/kg (SC) showed strong potentiation of capsaicin-induced secondary mechanical allodynia. Furthermore, Pentoxyverine in vivo data indicates that oral administration of 50 mg/kg for 7 days in mice (22-25 g) significantly increased the latent period of aqueous ammonia-induced cough by 121.72% and inhibited cough frequency by 45.45% when used as a positive control. These results highlight its efficacy in weakening the cough reflex and promoting bronchial smooth muscle relaxation. In conclusion, Pentoxyverine is a potent $\sigma_1$ receptor agonist with significant potential for research into respiratory and nociceptive modulation.
Keywords
Pentoxyverine, 23142-01-0, Carbetapentane, Sigma Receptor, mAChR, Muscarinic acetylcholine receptor, sigma-1 receptor, σ1, σ2, muscarinic, antitussive, anticonvulsant, spasmolytic, bronchial interceptor, cough reflex, bronchial smooth muscle relaxation, airway resistance, Inhibitor, inhibitor, inhibit
References
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