5-Hydroxytryptamine antagonists and the 5-methoxy-N,N-dimethyltryptamine-induced changes of postdecapitation convulsions.
Pharmacology & toxicology January 1, 1987 DOI: 10.1111/j.1600-0773.1987.tb01716.x via PubMed
Summary
AI-generated from the abstractSeveral compounds that block serotonin (5-HT) receptors were tested for their ability to counteract changes in postdecapitation convulsions (PDCs) caused by 5-MeODMT, a serotonin agonist. Mianserin, methergoline, cinanserin, and methysergide substantially reduced the 5-MeODMT-induced prolongation of the time before convulsions began (latency) and, to a lesser extent, the duration of convulsions. Their effectiveness ranked mianserin > cinanserin > methysergide > methergoline. Pirenperone (a 5-HT2 antagonist) and pimozide (a dopamine antagonist) did not block these effects. When given alone, mianserin, methergoline, cinanserin, and methysergide prolonged convulsion duration but not latency; pirenperone prolonged both; pimozide had no effect. This suggests that 5-MeODMT's effects on PDCs are mediated through 5-HT1 receptors, offering a reliable model for studying spinal function.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats (implied by standard convulsion model) |
| Interventions | 5-MeODMT mianserin methergoline cinanserin methysergide pirenperone pimozide |
| Dose | 0.5 to 4.0 mg/kg 5-MeODMT, 0.25 mg/kg pirenperone, 0.5-2.0 mg/kg pimozide |
| Citations | 2 |
| Key finding | 5-MeODMT-induced changes in postdecapitation convulsions appear to be mediated via 5-HT1 receptors, as they are blocked by certain 5-HT antagonists but not by a 5-HT2 or dopamine antagonist. |
Abstract
The ability of various compounds to antagonise the 5-MeODMT induced prolongations of latency and duration of postdecapitation convulsions (PDCs) were compared. The 5-hydroxytryptamine (5-HT) receptor antagonists, mianserin, methergoline, cinanserin and methysergide antagonised the 5-MeODMT (0.5 to 4.0 mg/kg) induced prolongations of latency to onset of convulsions substantially and to a lesser extent the prolongation of duration. The efficacy of the 5-HT antagonists for blocking 5-MeODMT changes of PDCs was roughly of the order mianserin greater than cinanserin greater than methysergide greater than methergoline. Pirenperone, the 5-HT2 antagonist, and pimozide, the dopamine receptor antagonist did not antagonise the 5-MeODMT induced changes. Mianserin, methergoline, cinanserin and methysergide, by themselves, prolonged the duration of PDCs but did not affect latency. Pirenperone (0.25 mg/kg) prolonged both the latency and duration of the PDCs while pimozide (0.5-2.0 mg/kg) had no effect upon PDCs. This evidence suggests that 5-MeODMT induced changes of PDCs are mediated via 5-HT1 receptors and thus a reliable model to combine with other measures of spinal function is suggested.