Further studies on the dose-dependent stimulus properties of 5-methoxy-N,N-dimethyltryptamine.
Pharmacology, biochemistry, and behavior – December 01, 1986
Source: PubMed
Summary
A compelling finding reveals that cyproheptadine completely blocked the effects of 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) in a study involving 22 rats. In contrast, cinanserin and methergoline only partially attenuated the drug’s effects, while methysergide had minimal impact. When the dosage increased to 3.0 mg/kg, methysergide and methergoline showed partial blockage, but cyproheptadine and cinanserin did not significantly alter responses. These outcomes highlight the need for caution in interpreting studies using these serotonin antagonists with 5-OMe DMT.
Abstract
Twenty-two rats were trained to discriminate either 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a standard two-lever operant procedure. Once responding was stable, various doses of several serotonin (5-HT) antagonists, i.e., cyproheptadine (CYP), methysergide (UML), cinanserin (CIN), and methergoline (MCE), were administered in combination with 5-OMe DMT, to assess the ability of each antagonist to attenuate each 5-OMe DMT-stimulus. The 5-OMe DMT-stimulus at 1.5 mg/kg was completely antagonized by CYP, and was partially attenuated by CIN and MCE. UML had negligible effects on 5-OMe DMT-appropriate responding. In the 3.0 mg/kg 5-OMe DMT-trained rats, UML and MCE partially blocked the 5-OMe DMT-stimulus; CYP and CIN had no significant effect on 5-OMe DMT-appropriate responding. The results suggest that until the in vivo effects and mechanism of action of 5-OMe DMT and certain 5-HT antagonists are better understood, caution is advised when conclusions are drawn from studies employing these agents.