HETEROCYCLES FUSED TO A BENZENE RING
447
Migraine headaches that do not respond to analgesics may be relieved by the use of an agonist of the 5-HT 1
receptor, since these receptors are known to mediate vasoconstriction. Though the causes of migraine are not
clear, they are characterized by dilation of cerebral blood vessels. 5-HT 1 agonists based on the 5-HT structure in
current use include the sulfonamide derivative sumatriptan, and the more recent agents naratriptan, rizatriptan
and zolmitriptan. These are of considerable value in treating acute attacks.
N
H
Me
N
MeNHSO 2
N
H
NMe 2
N
N
H
NMe 2
Me 2 NSO 2
N
H
NMe 2
sumatriptan
O
NH
naratriptan
rizatriptan
O
zolmitriptan
N
N
Several of the ergot alkaloids also interact with 5-HT receptors. Some are used medicinally, but the most
notorious is the semi-synthetic derivative lysergic acid diethylamide (LSD). This is itself an indole derivative,
though the indole is part of a more complex fused-ring system. Nevertheless, from the structural similarities,
it is not difficult to see why LSD might trigger 5-HT receptors. It has the additional ability to interact with
noradrenaline and dopamine receptors, thus generating a complex pharmacological response. LSD is probably
the most powerful pyschotomimetic known, intensifying and distorting perceptions. Experiences can vary from
beautiful visions to living nightmares, and no two ‘trips’ are alike.
N
H
NH 2
HO
5-hydroxytryptamine
(serotonin; 5-HT)
N
H
NMe
H
O
NEt 2
lysergic acid diethylamide
(lysergide; LSD)
N
H
NMe
H
O
NEt 2
OH
OH
HO
NH 2
noradrenaline
(norepinephrine)
OH
OH
NH 2
dopamine
lysergic acid diethylamide
(lysergide; LSD)
Also known to be hallucinogenic are the indole derivatives psilocin and psilocybin found in the so-called
magic mushrooms, Psilocybe species. Ingestion of these small fungi causes visual hallucinations with rapidly
changing shapes and colours. Psilocybin is the phosphate of psilocin; although based on 4-hydroxytryptamine,
they also act on 5-HT receptors.
N
H
NHAc
MeO
melatonin
N
H
indole-3-acetic acid
CO 2 H
N
H
NH 2
OH
psilocin
N
H
NH 2
O
psilocybin
P
OH
HO
O
Melatonin is N-acetyl-5-methoxytryptamine, a simple derivative of serotonin. It is a natural hormone secreted
by the pineal gland in the brain during the hours of darkness. It is involved in controlling the body’s day–night
447
Migraine headaches that do not respond to analgesics may be relieved by the use of an agonist of the 5-HT 1
receptor, since these receptors are known to mediate vasoconstriction. Though the causes of migraine are not
clear, they are characterized by dilation of cerebral blood vessels. 5-HT 1 agonists based on the 5-HT structure in
current use include the sulfonamide derivative sumatriptan, and the more recent agents naratriptan, rizatriptan
and zolmitriptan. These are of considerable value in treating acute attacks.
N
H
Me
N
MeNHSO 2
N
H
NMe 2
N
N
H
NMe 2
Me 2 NSO 2
N
H
NMe 2
sumatriptan
O
NH
naratriptan
rizatriptan
O
zolmitriptan
N
N
Several of the ergot alkaloids also interact with 5-HT receptors. Some are used medicinally, but the most
notorious is the semi-synthetic derivative lysergic acid diethylamide (LSD). This is itself an indole derivative,
though the indole is part of a more complex fused-ring system. Nevertheless, from the structural similarities,
it is not difficult to see why LSD might trigger 5-HT receptors. It has the additional ability to interact with
noradrenaline and dopamine receptors, thus generating a complex pharmacological response. LSD is probably
the most powerful pyschotomimetic known, intensifying and distorting perceptions. Experiences can vary from
beautiful visions to living nightmares, and no two ‘trips’ are alike.
N
H
NH 2
HO
5-hydroxytryptamine
(serotonin; 5-HT)
N
H
NMe
H
O
NEt 2
lysergic acid diethylamide
(lysergide; LSD)
N
H
NMe
H
O
NEt 2
OH
OH
HO
NH 2
noradrenaline
(norepinephrine)
OH
OH
NH 2
dopamine
lysergic acid diethylamide
(lysergide; LSD)
Also known to be hallucinogenic are the indole derivatives psilocin and psilocybin found in the so-called
magic mushrooms, Psilocybe species. Ingestion of these small fungi causes visual hallucinations with rapidly
changing shapes and colours. Psilocybin is the phosphate of psilocin; although based on 4-hydroxytryptamine,
they also act on 5-HT receptors.
N
H
NHAc
MeO
melatonin
N
H
indole-3-acetic acid
CO 2 H
N
H
NH 2
OH
psilocin
N
H
NH 2
O
psilocybin
P
OH
HO
O
Melatonin is N-acetyl-5-methoxytryptamine, a simple derivative of serotonin. It is a natural hormone secreted
by the pineal gland in the brain during the hours of darkness. It is involved in controlling the body’s day–night