Topic
Inaperisone
About: Inaperisone is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 79 citations. The topic is also known as: 1-(4-Ethylphenyl)-2-methyl-3-(1-pyrrolidinyl)-1-propanone.
Papers
TL;DR: The data suggest that tolperisone-type muscle relaxants exert their spinal reflex inhibitory action predominantly via a presynaptic inhibition of the transmitter release from the primary afferent endings via a combined action on voltage-gated sodium and calcium channels.
Abstract: The spinal reflex depressant mechanism of tolperisone and some of its structural analogs with central muscle relaxant action was investigated. Tolperisone (50–400 μM), eperisone, lanperisone, inaperisone, and silperisone (25–200 μM) dose dependently depressed the ventral root potential of isolated hemisected spinal cord of 6-day-old rats. The local anesthetic lidocaine (100–800 μM) produced qualitatively similar depression of spinal functions in the hemicord preparation, whereas its blocking effect on afferent nerve conduction was clearly stronger. In vivo, tolperisone and silperisone as well as lidocaine (10 mg/kg intravenously) depressed ventral root reflexes and excitability of motoneurons. However, in contrast with lidocaine, the muscle relaxant drugs seemed to have a more pronounced action on the synaptic responses than on the excitability of motoneurons. Whole-cell measurements in dorsal root ganglion cells revealed that tolperisone and silperisone depressed voltage-gated sodium channel conductance at concentrations that inhibited spinal reflexes. Results obtained with tolperisone and its analogs in the [3H]batrachotoxinin A 20-α-benzoate binding in cortical neurons and in a fluorimetric membrane potential assay in cerebellar neurons further supported the view that blockade of sodium channels may be a major component of the action of tolperisone-type centrally acting muscle relaxant drugs. Furthermore, tolperisone, eperisone, and especially silperisone had a marked effect on voltagegated calcium channels, whereas calcium currents were hardly influenced by lidocaine. These data suggest that tolperisone-type muscle relaxants exert their spinal reflex inhibitory action predominantly via a presynaptic inhibition of the transmitter release from the primary afferent endings via a combined action on voltage-gated sodium and calcium channels.
66 citations
Journal Article•
TL;DR: A physiologically-based pharmacokinetic model of IPS combined with its pharmacological effect in rats is developed, which could simulate the concentration-dependent changes in blood flow rates based on the drug concentrations at the site of action.
Abstract: This study was designed to develop a physiologically-based pharmacokinetic/pharmacodynamic model for drugs whose pharmacokinetics are influenced by their dose-dependent pharmacological effects. Since blood flow rate is one of the important factors that determine the distribution and elimination processes of drugs, we used inaperisone [IPS, (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)-propiophenone hydrochloride], a novel centrally acting muscle relaxant that has been found by us to significantly alter muscle and fat blood flow rates in a dose-dependent manner, as a model compound. With regard to the changes in muscle blood flow rate exhibited by IPS, the brain was shown to be the major site of action based on changes in the observed blood flow rates, determined by the 51Cr-labeled microsphere method, in rats injected iv and intracerebroventricularly with various doses of IPS. Consequently, the blood flow rates in the muscle and fat were well correlated with the concentration of IPS in the brain using Hill's equation. Moreover, hepatic and renal intrinsic clearances of IPS at steady-state were determined by the constant iv infusion method. The saturation of in vivo hepatic and renal metabolisms of IPS was found at venous plasma concentrations higher than 1 microgram/ml. Taken all together, we developed a physiologically-based pharmacokinetic model of IPS combined with its pharmacological effect in rats, which could simulate the concentration-dependent changes in blood flow rates based on the drug concentrations at the site of action.(ABSTRACT TRUNCATED AT 250 WORDS)
17 citations
TL;DR: From results, it is speculated that, among other possible mechanisms, inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem.
13 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2005 | 1 |
| 1992 | 1 |
| 1990 | 1 |