Mechanism of verapamil calcium channel blockade-induced hyperprolactinemia.
Verapamil, a phenylalkylamine calcium channel blocker, causes a doubling of serum prolactin (PRL) levels in humans. To determine whether the mechanism involved a decrease in the PRL response to dopamine (DA), we infused low doses of DA, finding that the percent inhibition of PRL was not affected by verapamil (max %decrements for 0.003, 0.01, and 0.03 microgram.kg-1.min-1 doses of DA, respectively, 86.7 +/- 19.1, 73.2 +/- 24.8, and 65.2 +/- 20.0% without verapamil and 93.4 +/- 24.6, 79.7 +/- 14.9, and 58.0 +/- 18.1% with verapamil). To determine whether the PRL elevation was due to a decrease in hypothalamic generation of DA, we measured the inhibition of PRL by L-dopa before and after inhibition of peripheral decarboxylase activity with carbidopa. Without verapamil, L-dopa alone and carbidopa-L-dopa caused similar maximum decreases in PRL levels of 83.2 +/- 2.5 and 80.3 +/- 2.0%, respectively. With verapamil, the PRL maximum decrement with L-dopa was 85.2 +/- 2.7% and with carbidopa-L-dopa was 76.3 +/- 1.9% (P < 0.01). We also found that dihydropyridine and benzothiazepine calcium channel blockers had no effect on PRL. These results suggest that verapamil acts by decreasing central DA generation, possibly through N-type calcium channels.
Kelley
S R
SR
Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Kamal
T J
TJ
Molitch
M E
ME
D000293:Adolescent; D000328:Adult; D002121:Calcium Channel Blockers; D002230:Carbidopa / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D014700:Verapamil
D002121:Calcium Channel Blockers; D007980:Levodopa; D011388:Prolactin; D014700:Verapamil; D002230:Carbidopa; D004298:Dopamine