35
Southeastern pygmy rattlesnake led to the discovery of eptifibatide. The drugs are called
“super aspirins” because they are more potent than aspirin. Both were approved by FDA
in 1998, indicated for treating unstable angina and angioplasty.
Venoms and Toxins
Because exenatide and ziconotide represent new drug classes, they will be the impetus for
a frenzy of additional active research by biotechnology and pharmaceutical companies.
Venoms are proving to be a remarkable source of novel peptides that have potential appli-
cations in human health. Venoms are rarely pure substances. In most cases they represent
mixtures of numerous compounds, or toxins, which may have toxic and other properties.
Toxins are compounds deleterious to other organisms at a certain dosage. They interfere
with important physiological plant, animal or human activities, causing envenoming or
poisoning. A number of these toxins already have been used in vivo for proof-of-concept
studies, some having undergone preclinical or clinical development for treating pain, dia-
betes, multiple sclerosis and cardiovascular diseases.6 Toxins that target ion channels and
receptors have been isolated from spiders, marine snails, snakes, scorpions and a range
of other animals.7 Snake toxins have been studied extensively, including their molecular
origins, chemical nature and biologic activities. These toxins are made from the same basic
molecules as the proteins of the human body.8 They contain short chains of amino acids,
called peptides, which poison the victim by causing paralysis. Many act like curare, and
block the action of acetylcholine at the junction between the nerve and muscle.9 Due to
their relatively large size, hydrophilic nature and susceptibility to hydrolysis in the stom-
ach, the oral bioavailability of venom peptides (from 10 to 40 amino acids) is generally
poor. This means that peptides must be administered to the site of action by either intrave-
nous, intrathecal, intraperitoneal, intramuscular, subcutaneous or epidural injection.
Snakes
Venomous snakes are known to possess one of the most sophisticated integrated weap-
ons systems in the natural world.10 Snakes produce venoms in highly specialized glands
on either side of their upper jaws. When they strike, snakes squeeze the glands and the
venom is released through hollow teeth.
Cone Snails
Cone snails possess a very complex venom apparatus, located in the posterior part of
the body. Venom, injected into the prey using a harpoon-tipped proboscis, is a mixture
of biologically highly active protein-toxins. Like snakes, Conus venoms also contain a
remarkable diversity of pharmacologically active small peptides. Their targets are ion
channels and receptors in the neuromuscular system. These high-affinity peptides act on
voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA)
receptors, acetylcholine and vasopressor receptors.11 The toxic components from the
venom of C. magus, the original source of ziconotide, consist of 13 to 29 amino acids.12
Envenomation by cone snails is known to cause death in humans.
Gila Monster
The Gila monster is a large, stout lizard with a fat tail, whose body is covered with thick,
scale-like beads. It belongs to a class of reptiles that includes more than 2,000 lizard
species. Gila monster (Heloderma suspectum) and H. horridum are the only two that are
venomous. Their venom glands are located on the anterior sides of the lower jaws. Venom
is discharged at the base of the teeth, mixed with saliva and enters the wound by capil-
lary action along the grooves of the teeth. Dr. Mitchell was correct the venom, a mixture
Venoms and Toxins
Southeastern pygmy rattlesnake led to the discovery of eptifibatide. The drugs are called
“super aspirins” because they are more potent than aspirin. Both were approved by FDA
in 1998, indicated for treating unstable angina and angioplasty.
Venoms and Toxins
Because exenatide and ziconotide represent new drug classes, they will be the impetus for
a frenzy of additional active research by biotechnology and pharmaceutical companies.
Venoms are proving to be a remarkable source of novel peptides that have potential appli-
cations in human health. Venoms are rarely pure substances. In most cases they represent
mixtures of numerous compounds, or toxins, which may have toxic and other properties.
Toxins are compounds deleterious to other organisms at a certain dosage. They interfere
with important physiological plant, animal or human activities, causing envenoming or
poisoning. A number of these toxins already have been used in vivo for proof-of-concept
studies, some having undergone preclinical or clinical development for treating pain, dia-
betes, multiple sclerosis and cardiovascular diseases.6 Toxins that target ion channels and
receptors have been isolated from spiders, marine snails, snakes, scorpions and a range
of other animals.7 Snake toxins have been studied extensively, including their molecular
origins, chemical nature and biologic activities. These toxins are made from the same basic
molecules as the proteins of the human body.8 They contain short chains of amino acids,
called peptides, which poison the victim by causing paralysis. Many act like curare, and
block the action of acetylcholine at the junction between the nerve and muscle.9 Due to
their relatively large size, hydrophilic nature and susceptibility to hydrolysis in the stom-
ach, the oral bioavailability of venom peptides (from 10 to 40 amino acids) is generally
poor. This means that peptides must be administered to the site of action by either intrave-
nous, intrathecal, intraperitoneal, intramuscular, subcutaneous or epidural injection.
Snakes
Venomous snakes are known to possess one of the most sophisticated integrated weap-
ons systems in the natural world.10 Snakes produce venoms in highly specialized glands
on either side of their upper jaws. When they strike, snakes squeeze the glands and the
venom is released through hollow teeth.
Cone Snails
Cone snails possess a very complex venom apparatus, located in the posterior part of
the body. Venom, injected into the prey using a harpoon-tipped proboscis, is a mixture
of biologically highly active protein-toxins. Like snakes, Conus venoms also contain a
remarkable diversity of pharmacologically active small peptides. Their targets are ion
channels and receptors in the neuromuscular system. These high-affinity peptides act on
voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA)
receptors, acetylcholine and vasopressor receptors.11 The toxic components from the
venom of C. magus, the original source of ziconotide, consist of 13 to 29 amino acids.12
Envenomation by cone snails is known to cause death in humans.
Gila Monster
The Gila monster is a large, stout lizard with a fat tail, whose body is covered with thick,
scale-like beads. It belongs to a class of reptiles that includes more than 2,000 lizard
species. Gila monster (Heloderma suspectum) and H. horridum are the only two that are
venomous. Their venom glands are located on the anterior sides of the lower jaws. Venom
is discharged at the base of the teeth, mixed with saliva and enters the wound by capil-
lary action along the grooves of the teeth. Dr. Mitchell was correct the venom, a mixture
Venoms and Toxins