Reduction of hyperglycemia after oral glucose load by the new alpha 2-adrenergic receptor antagonist SL 84.0418 in healthy subjects.
OBJECTIVE
To assess the antihyperglycemic activity of a new peripherally acting alpha 2-adrenergic receptor antagonist, SL 84.0418 in healthy volunteers


METHODS
This was a randomized, double-blind crossover study. The effects of 10, 50, and 100 mg SL 84.0418 on blood glucose, plasma insulin, C-peptide, glucagon, epinephrine, and norepinephrine were investigated in comparison with placebo and 5 mg glipizide before and after an oral glucose challenge (75 gm).


RESULTS
Peak blood glucose and area under the blood-glucose curve were dose-dependently reduced by SL 84.0418; the extent of this reduction was similar with 100 mg SL 84.0418 and glipizide. Glipizide but not SL 84.0418 decreased nadir blood glucose. Plasma insulin and C-peptide were increased by glipizide but not by SL 84.0418. Treatments did not modify plasma glucagon. Plasma epinephrine increased during glipizide treatment and plasma norepinephrine increased during treatment with 50 and 100 mg SL 84.0418. Systolic and diastolic blood pressure were moderately enhanced by 50 and 100 mg SL 84.0418. Adverse effects reflecting alpha 2-adrenergic receptor blockade occurred more frequently with 100 mg SL 84.0418. The adverse effect profile of 50 mg SL 84.0418 was not different from that observed with glipizide.


CONCLUSIONS
The alpha 2-adrenergic receptor antagonist SL 84.0418 dose dependently reduced the increase in blood glucose after glucose load without modification of plasma insulin. It may represent an alternative to sulfonylureas in the treatment of non-insulin-dependent diabetes mellitus. Further studies are needed to assess its efficacy and tolerability in non-insulin-dependent patients.
Berlin
I
I
Department of Clinical Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
Rosenzweig
P
P
Chalon
S
S
Fuseau
E
E
Landault
C
C
Cesselin
F
F
Blacker
C
C
Puech
A J
AJ
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005913:Glipizide / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D002096:C-Peptide; D002395:Catecholamines; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D011758:Pyrroles; C074936:SL 84.0418; D005934:Glucagon; D005913:Glipizide