Neurotopia

Looks like yet another interesting toxin was found, this time in a venomous snail. This discovery comes from the lab of an old player in the field, who apparently discovered the conotoxin that is used in Prialt.

McIntosh says the OmIA toxin will be useful in designing new medicines because it fits like a key into certain lock-like “nicotinic acetylcholine receptors” found on nerve cells in the brain and the rest of the nervous system.

“Those are the same types of receptors you activate if you smoke a cigarette,” he says, explaining that nicotine in cigarette smoke “binds” to the receptor to trigger the release of a neurotransmitter, which is a chemical that carries a nerve impulse from one nerve cell to another, allowing nerve cells to communicate.

“Nicotine acts on those receptors in our brain, but they are in our brain for better reasons than to enjoy a cigarette,” McIntosh says. Different forms or subtypes of nicotinic receptors control the release of different neurotransmitters. “That’s important because if you had compounds to facilitate the release of one neurotransmitter and not another neurotransmitter, that opens up medicinal potential,” he says.

“For instance, one receptor modifies the release of dopamine. There are inadequate amounts of dopamine in Parkinson’s disease,” so a medicine designed to fit into a certain subtype of nicotinic receptor would produce more dopamine and thus protect against the development of tremors and other Parkinson’s symptoms. Indeed, other studies have found that smoking seems to forestall Parkinson’s disease.

A medicine that could block certain nicotinic receptors could be used to help people stop smoking cigarettes, and the same method might work for alcoholism because nicotinic receptors may be involved in alcohol addiction, McIntosh says.

Other nicotinic receptors trigger the release of neurotransmitters involved in memory, so activating the right receptors might lessen Alzheimer’s memory loss.

“One reason people smoke is they feel their thinking may be a little better, with increased attention and focus,” McIntosh says, noting that pharmaceutical companies “would like to mimic that positive benefit without all the downsides of cigarette smoke.”

Other nicotinic receptors influence “the release of serotonin and norepinephrine, two neurotransmitters strongly implicated in mood disorders” such as depression, so a drug to activate those receptors might treat depression, he adds.

Schizophrenics tend to smoke heavily because something in cigarette smoke “seems to help them filter out irrelevant stimuli. They can focus better,” McIntosh says. So a drug aimed at certain nicotinic receptors might treat schizophrenia.

The interesting part is how these toxins are put to use, parsing out the actions of different receptor subtypes.

McIntosh says the new toxin itself is unlikely to become a drug because it blocks rather than stimulates nicotinic receptors. But because it can act on some types of nicotinic receptors and not others – like a key that opens some locks but not others – it has great potential as a tool for precisely identifying the shape and structure of the receptor “locks,” thus making it easier to design new medicines or “keys” to fit those receptors and trigger them to release desired neurotransmitters.

In the new study, about 70 compounds from numerous cone snail species were screened in collaboration with Taylor’s lab at the University of California, San Diego.

Taylor uses “acetylcholine binding protein” as a model for nicotinic receptors. In other words, cone snail toxin “keys” that fit into nicotinic receptor “locks” also fit into highly similar “locks” made of this binding protein. So the binding protein was used as a way to find toxins that also would fit into nicotinic receptors. The new OmIA toxin was most interesting because it tightly fits some nicotinic receptors but not others. A drug that tightly fits desired receptors but not others is less likely to have undesirable side effects.

So much of our knowledge in the realm of neuroscience comes from the study of toxins and other natural compounds; in recognition of this fact, we often name receptors for the compounds that help us isolate them, such as nicotinic and muscarinic receptors.

I cannot emphasize enough the importance of maintaining biodiversity. Who knows what classes of therapeutics are out there, just waiting to be discovered because of compounds like this?