Pyridoindole stobadine is a nonselective inhibitor of voltage-operated ion channels in rat sensory neurons.
Pyridoindole stobadine, a compound with known neuroprotective, antioxidant, oxygen-free radical scavenging and antiarrhythmic properties, was analysed as to its effect on inward sodium and calcium currents (INa and ICa), respectively, and on fast inactivating and slow non-inactivating components of potassium outward current (IKf and IKs), respectively, in the neuronal membrane. A voltage-clamp technique was used in internally dialyzed single neurons isolated from young rat sensory ganglia. Stobadine inhibited all currents studied in a concentration dependent manner (0.1-3 mmol/l). Apparent affinity constants pD'2,--(i.e. negative logarithm of IC50) were 3.147 +/- 0.030, 3.112 +/- 0.084, 3.089 +/- 0.062 and 2.918 +/- 0.059 for INa, IKs, IKf, and ICa, respectively. Full current inhibition occurred only in INa at concentrations of > 1 and < or = 3 mmol/l. Saturation of the inhibition of both components of IK at approximately 40% of the control level occurred at concentrations > 1 mmol/l. Stobadine was found to be a nonspecific inhibitor of the currents studied. This property as well as the range of pD'2, values are comparable to those observed in the local anesthetics procaine and trimecaine. The inhibition of voltage-operated ion channels in membranes of excitable cells by stobadine might be responsible for its capability to inhibit synaptic transmission and axonal conduction. It might participate also in the antidysrrhythmic effect of stobadine.
Stolc
S
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Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D017950:Ganglia, Sensory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D026941:Sodium Channel Blockers; D009435:Synaptic Transmission / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002243:Carbolines; D016166:Free Radical Scavengers; D007473:Ion Channels; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; C100106:dicarbine