Mechanisms involved in the hyperglycemic effect of the 5-HT1C/5-HT2 receptor agonist, DOI

Eur J Pharmacol. 1992 Mar 17;213(1):41-6. doi: 10.1016/0014-2999(92)90230-2.


Previous experiments have indicated that 5-HT2 receptors and catecholaminergic systems mediate the rise in plasma glucose levels elicited by acute administration of the 5-HT1c/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). On this basis, we investigated the location of these serotonin receptors and the nature of this catecholaminergic involvement. Administration of DOI (0.4 mg/kg i.v.) to conscious rats (bearing jugular catheters) elicited a rapid rise in plasma glucose which was associated with a decreased insulin response to a glucose bolus (300 mg/kg i.v.). Pretreatment with the peripherally acting 5-HT1c/5-HT2 receptor antagonist, BW 501C67 (0.5 mg/kg i.v. 10 min beforehand) prevented the rise in plasma glucose triggered by the peripherally acting 5-HT1c/5-HT2 receptor agonist, alpha-methyl-5-HT (0.75 mg/kg i.v.), but amplified the rise elicited by DOI. Pretreatment with chlorisondamine (1 mg/kg i.v. 10 min beforehand) or adrenalectomy 20 h beforehand prevented the DOI-induced hyperglycemia. On the other hand, pretreatment with dexamethasone (0.35 mg/kg s.c. 2 h and 20 min beforehand) did not affect the DOI-induced hyperglycemia. It is concluded that the hyperglycemic effect of DOI administration is mediated by centrally located 5-HT2 receptors and, in turn, adrenal epinephrine release.

MeSH terms

  • Adrenalectomy
  • Amidines / pharmacology
  • Amphetamines / administration & dosage
  • Amphetamines / pharmacology*
  • Animals
  • Blood Glucose / analysis*
  • Chlorisondamine / pharmacology
  • Dexamethasone / pharmacology
  • Drug Interactions
  • Hyperglycemia / chemically induced
  • Hyperglycemia / metabolism*
  • Injections, Intravenous
  • Insulin / metabolism
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology


  • Amidines
  • Amphetamines
  • Blood Glucose
  • Insulin
  • Receptors, Serotonin
  • Serotonin Antagonists
  • BW 501C
  • Dexamethasone
  • Chlorisondamine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine