Antagonism of 5-methoxy-N,N-dimethyltryptamine-induced changes in postdecapitation convulsions in rats by repeated treatment with drugs enhancing 5-hydroxytryptamine neurotransmission.
The Journal of pharmacy and pharmacology – September 01, 1985
Source: PubMed
Summary
Repeated administration of specific drugs significantly reduced the latency and duration of postdecapitation convulsions (PDCs) induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). In a study involving multiple compounds, Zimelidine, fluoxetine, and amiflamine effectively blocked PDC effects, while alaproclate and others showed lesser impact. Notably, repeated doses of 5-MeODMT completely negated its acute effects. These results suggest that down-regulation of serotonin receptors may play a crucial role in modulating these responses, providing insights into receptor sensitivity changes at the spinal level.
Abstract
Repeated administration of drugs that increase tryptaminergic neurotransmission antagonized the increase in latency to onset and the duration of postdecapitation convulsions (PDCs) induced by an acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) injection; Zimelidine (2 X 5 mg kg-1), fluoxetine (2 X 5 mg kg-1), amiflamine (2 X 2.5 mg kg-1) and alpha-ethyltryptamine (2 X 2.5 mg kg-1) administered orally over 10 days caused a substantial blockade of the increase in latency to onset and duration of PDCs following 5-MeODMT, whereas alaproclate (2 X 5 mg kg-1), clorgyline (1 X 1 mg kg-1) and pargyline (2 X 2.5 mg kg-1) caused a lesser blockade. Repeated 5-MeODMT (3 X 2 mg kg-1) administration blocked the acute effects of 5-MeODMT (2 and 4 mg kg-1) upon PDCs completely. These findings indicate down-regulation of the 5-hydroxytryptamine receptors which mediate the action of 5-MeODMT on the PDCs and offer a simple model system for studying 5-HT receptor sensitivity changes at the spinal level.