Effects of the 5-HT1C/5-5-HT2 receptor agonists DOI and alpha-methyl-5-HT on plasma glucose and insulin levels in the rat

Eur J Pharmacol. 1990 Oct 23;187(3):435-43. doi: 10.1016/0014-2999(90)90370-l.


Administration of the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane (DOI, 0.125-2.0 mg/kg i.v.) triggered dose-dependent increases in plasma glucose; plasma insulin levels remained unchanged. Pretreatment with the 5-HT1C/5-HT2 receptor antagonists LY 53857, ritanserin, or the mixed 5-HT2/alpha 1-adrenoceptor antagonist ketanserin either diminished or prevented the hyperglycemic effect of DOI (0.5 mg/kg). Administration of the mixed 5-HT1C receptor agonists/5-HT2 receptor antagonists 1-(3-chlorophenyl)-piperazine (mCPP) or 1-(3-trifluoromethyl)phenyl)piperazine level (TFMPP) did not affect plasma glucose levels. However, pretreatment with mCPP or TFMPP decreased DOI-induced hyperglycemia in a dose-dependent manner. The alpha 2-adrenoceptor antagonist idazoxan and the ganglionic blocker hexamethonium both decreased DOI-induced hyperglycemia, Whilst the alpha 1-adrenoceptor antagonist prazosin amplified the rise in plasma glucose elicited by DOI. The peripherally acting 5-HT1C/5-HT2 receptor agonist alpha-methyl-5-HT (0.5-1.0 mg/kg i.v.) triggered a rise in plasma glucose levels that was associated with an increase in plasma insulin levels. Pretreatment with LY 53857 diminished alpha-methyl-5-HT-induced hyperglycemia. These data indicate that 5-HT2 receptors, but not 5-HT1C receptors, and catecholaminergic systems, mediate DOI-induced hyperglycemia. Moreover, it is suggested that the inhibition of insulin release by DOI is centrally mediated, and that activation of peripheral 5-HT2 receptors may affect glycemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology*
  • Animals
  • Blood Glucose / metabolism*
  • Catecholamines / blood
  • Ergolines / pharmacology
  • Hyperglycemia / blood
  • Hyperglycemia / chemically induced
  • Insulin / blood*
  • Male
  • Piperazines / pharmacology
  • Piperidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects*
  • Ritanserin
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology


  • Amphetamines
  • Blood Glucose
  • Catecholamines
  • Ergolines
  • Insulin
  • Piperazines
  • Piperidines
  • Receptors, Serotonin
  • Ritanserin
  • alpha-methylserotonin
  • 1-(3-trifluoromethylphenyl)piperazine
  • Serotonin
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • LY 53857
  • 4-iodo-2,5-dimethoxyphenylisopropylamine