Int Neurourol J.  2018 Dec;22(4):252-259. 10.5213/inj.1836146.073.

Effects of High Concentrations of Naftopidil on Dorsal Root-Evoked Excitatory Synaptic Transmissions in Substantia Gelatinosa Neurons In Vitro

• Uta D
• Hattori T
• Yoshimura

• KMID: 2431866
• DOI: http://doi.org/10.5213/inj.1836146.073

Abstract

PURPOSE
Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated.
METHODS
Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively.
RESULTS
Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs.
CONCLUSIONS
The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

Keyword

Adrenergic alpha1 receptor antagonists; Excitatory postsynaptic currents; Naftopidil; Substantia gelatinosa

MeSH Terms

Adult
Animal Experimentation
Animals
Asian Continental Ancestry Group
Baths
Excitatory Postsynaptic Potentials
Humans
In Vitro Techniques*
Inhibitory Postsynaptic Potentials
Injections, Spinal
Lower Urinary Tract Symptoms
Male
Nerve Fibers, Unmyelinated
Neurons*
Prazosin
Prostatic Hyperplasia
Rats
Rats, Sprague-Dawley
Reflex
Spinal Cord
Substantia Gelatinosa*
Urinary Bladder
Urination
Prazosin