Effect of L-type calcium channel antagonists on spermine-induced CNS excitation in vivo.
The ability of nitrendipine, nisoldipine, verapamil and gabapentin to inhibit the development of CNS excitation induced by spermine was assessed in mice. Injection of an excitotoxic dose of spermine (100 microg, i.c.v.) in mice results in worsening tremor that culminates in the development of a fatal tonic convulsion within 8 h of spermine administration. The dihydropyridines, nitrendipine and nisoldipine, which are L-type calcium channel antagonists acting at the alpha1 subunit, inhibited the development of spermine-induced effects. Verapamil, which also acts at the alpha1 subunit of the L-type calcium channel, also inhibited the development of spermine-induced CNS excitation. Gabapentin, a postulated L-type calcium channel antagonist interacting at the alpha2delta subunit, did not inhibit the development of spermine-induced effects. These results show that antagonists of the alpha1 subunit of L-type calcium channels can effectively inhibit the effects of spermine in vivo. This may highlight the importance of L-type calcium channels in spermine action.
Doyle
Karen M
KM
Department of Pharmacology, School of Pharmacy, Trinity College, Dublin 2, Ireland. karen.doyle@nuigalway.ie
Kirby
Brian P
BP
Murphy
Desiree
D
Shaw
Graham G
GG
D000588:Amines / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D000077206:Gabapentin; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015737:Nisoldipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D013096:Spermine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D013096:Spermine; D015737:Nisoldipine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009568:Nitrendipine; D014700:Verapamil