Biomedical Engineering Reference
In-Depth Information
17.4 THE HISTAMINE H
3
RECEPTOR: MOLECULAR
ASPECTS AND SELECTIVE LIGANDS
17.4.1 M
OLECULAR
A
SPECTS
OF
THE
H
ISTAMINE
H
3
R
ECEPTOR
P
ROTEIN
The physiological role of histamine as a neurotransmitter became apparent in 1983, when Arrang
and coworkers discovered the inhibitory effect of histamine on its own release and synthesis in
the brain. This effect was not mediated by the known H
1
and H
2
receptor subtypes as no correla-
tion with either the H
1
or the H
2
receptor activity of known histaminergic ligands was observed.
Soon thereafter, the H
3
receptor agonist
R
-
-methylhistamine and the antagonist thioperamide
(see Figures 17.4 and 17.5, respectively) were developed, thereby coni rming that a new receptor
α
N
NH
2
NH
2
NH
2
N
N
N
N
CH
3
CH
3
CH
3
HN
HN
HN
HN
(
R
)-α-Methylhistamine
(eutomer)
(
S
)-α-Methylhistamine
(distomer)
N
α
-Methylhistamine
Histamine
N
N
N
S
NH
2
N
NH
N
N
HN
HN
HN
NH
HN
Imetit
Immepip
Immethridine
Methimepip
FIGURE 17.4
Reference histamine H
3
receptor agonists.
S
NH
I
N
H
NH
S
H
HN
S
H
HN
HN
N
N
Cl
N
Thioperamide
Clobenpropit
Iodophenpropit
R
O
HN
H
HN
HN
N
N
NH
N
I
R = H: Impentamine
VUF5681
Iodoproxyfan
CN
N
N
O
O
N
ABT-239
JNJ-5207852
CN
F
O
N
N
N
N
O
F
O
N
A-423579
GSK-189254
FIGURE 17.5
Histamine H
3
receptor antagonists and inverse agonists.
