Pharmaceuticals–Some Important Drugs - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 198

Pharmaceuticals) was approved in the U.S. in 2005 and is an injectable
39-amino acid synthetic peptide. It was originally identified in the saliva of
the Gila monster ( Heloderma suspectum) . Exenatide mimics the blood-sugar
lowering activity of glucagon-like peptide 1 (GLP-1) [48]. It affects pan-
creatic beta-cell responsiveness to glucose. This leads to insulin release,
predominantly in the presence of elevated glucose concentrations. Liraglutide
(Victoza ® , Novo Nordisk) is an analog of GLP-1. It was approved in the
U.S. in 2010. It is also a peptide and, like exenatide, promotes insulin release
in the presence of elevated glucose levels.
The DPP-4 enzyme inactivates incretin hormones such as GLP-1. Some
diabetes drugs work by inhibiting DPP-4 and therefore slow the inactivation
of incretin hormones. Sitagliptan (the phosphate salt is marketed as Januvia ® ,
Merck) and saxagliptin (Onglyza ® , Bristol-Myers Squibb) are examples of
DPP-4 inhibitors.

F

F

HO

NH 2 O

H

N

N

H 2 O

N H 2 O

H 3 PO 4 N

H 2 N

F N

O

CN

CF 3

Sitagliptan phosphate monohydrate Saxagliptan monohydrate

11.6 ANTIDEPRESSANTS

Major depressive disorder is among the most common psychiatric disorders
in the U.S. with an estimated prevalence of about 10% in the general popu-
lation [49]. The effects of antidepressants can be linked to the improvement
of neurotransmission by the monoamine neurotransmitters, serotonin, nore-
pinephrine, and dopamine [50].

NH 2

NH 2

NH 2

HO

HO HO

OH

HO

HO

H

Serotonin Norepinephrine Dopamine

Early antidepressant medications were called tricyclic antidepressants
(TCA), exemplified by dothiepin and amitriptyline. However, there are tox-
icity issues with these medications. The next generation of antidepressants
was the monoamine oxidase inhibitors (MAOIs). As their name implies,
they inhibit the monoamine oxidase enzyme thereby inhibiting the oxidation
of monoamines such as serotonin that act as neurotransmitters. Examples
include selegiline (available in transdermal patch form as Emsam ® , Somerset