oxytocin/antidiuretic activity ratio of 135,000:1, compared to the 200:1 ratio of the
natural hormone. On the other hand, the [1-deamino, D-Val^4 , D-Arg^4 ] VP has a 125,000:1
antidiuretic/pressor activity ratio (AVP has a 1:1 ratio). A few oxytocin inhibitors have
also been prepared, such as the [3, 5-dibromo-Tyr^2 ] OT, which inhibits the uterotonic
effect of the hormone.
5.17.4 Clinical Applications of OT and VPThe clinical applications of OT and vasopressin are widespread.
5.17.4.1 Clinical Uses of Oxytocin
Oxytocin is used to induce labor in childbirth and to promote the expulsion of the pla-
centa, although the antidiuretic activity of the native hormone is a disadvantage. Other
drugs with uterotonic activity include the ergot alkaloids.Ergot is from the fungus
Claviceps purpurea,which infects cereals, mainly rye. A number of indole alkaloids
have been isolated from this source, in which the indole moiety is lysergic acid. The
latter forms amides with both cyclic tripeptides (e.g.,ergocristine (5.77)) and with the
amino-alcohol L-alaninol in ergonovine (5.78). The peptide alkaloids have a slow and
cumulative action, whereas the water-soluble ergonovine and its derivatives are fast
acting. The latter is used to prevent postpartum hemorrhage by the compression of
uterine blood vessels through uterine muscle contraction. Some of these alkaloids are
α-adrenergic blocking agents and have been used with moderate success in the treat-
ment of migraine headaches.
5.17.4.2 Clinical Uses of Vasopressin
The treatment of diabetes insipidusis the most logical indication for vasopressin use.
Diabetes insipidus (not to be confused with diabetes mellitus, which arises from a defi-
ciency of insulin—frequently from pathology of the pancreas),is the disorder arising from
a deficiency of vasopressin—frequently from pathology of the posterior pituitary. From a
symptom perspective, both diabetes insipidus and mellitus are associated with polyuria
(passing large amounts of urine) and polydypsia (drinking large amounts of fluid).
HORMONES AND THEIR RECEPTORS 349