The following synthetic, structural analogs of
dopamine (DA) were examined for their ability to produce
hyperglycemia in conscious unrestrained rats: APO (
apomorphine),
RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane), di-n-propyldopamine, 2-di-n-propylamino-5,6-dihydroxytetralin, 2-dimethylamino-6,7-dihydroxytetralin,
lergotrile,
pergolide,
bromocriptine and
d-amphetamine. All the compounds demonstrated dose- and time-dependent hyperglycemic actions. The most potent DA analog to induce
hyperglycemia was 2-di-n-propylamino-5,6-dihydroxytetralin (0.18 mumol/kg) and, at the doses used, 2-dimethylamino-6,7-dihydroxytetralin produced the greatest elevation in
blood glucose (227% control). APO and
RDS-127 were used in experiments designed to provide additional mechanistic information concerning their hyperglycemic action. The
hyperglycemia produced by APO or
RDS-127 was blocked by
adrenalectomy, adrenodemedullation or prior administration of
pimozide, a DA receptor antagonist.
Phentolamine, an
alpha adrenergic receptor antagonist had no effect on the
hyperglycemia induced by APO or
RDS-127. Oral
glucose tolerance tests indicated that APO and
RDS-127 caused abnormal
glucose tolerance and inhibited the compensatory increase in serum immunoreactive
insulin. These effects were prevented by
pimozide or
phentolamine pretreatment. The potencies of the compounds to produce increases in serum
glucose concentrations (SG), inhibit the accumulation of
DOPA using the in vivo
gamma-butyrolactone procedure (
DOPA) and inhibit food intake (FI) were subjected to correlation analysis. Positive correlations were found for FI vs.
DOPA, r = 0.96; SG vs. decreases
DOPA, r = 0.98 and SG vs. FI, r = 0.98.(ABSTRACT TRUNCATED AT 250 WORDS)