Neuropeptides: Something to Sniff About Intranasal Drug Delivery Directly to the Brain

May 13, 2002 There are nasal sprays for allergies, colds, and sinus trouble. There may be a new use for nasal sprays: delivery of drugs to the brain. Neuropeptides are relatively large molecule neurotransmitters. Neurons use neurotransmitters to communicate with one another. Although neuropeptides could be used to treat neurological disorders, the development of therapies using these chemicals has been difficult because neuropeptides: 1) do not easily cross the blood-brain barrier (from the bloodstream into the brain). 2) may have significant side effects (e.g., weight gain, rash, cardiac problems) when they get into the blood. Researchers in Germany and the US think they have found a way to solve these problems: spray the neuropeptides up a patient's nose! The researchers tested the ability of three neuropeptides (insulin, vasopressin and melanocortin) to get into the cerebrospinal fluid (CSF) and blood supply. CSF and blood samples were taken from 36 subjects for 80 minutes after the neuropeptides were inhaled. The CSF levels of all three neuropeptides began to rise within 10 minutes after the chemicals were inhaled. The CSF levels of insulin and melanocortin peaked within 30 minutes, while that of vasopressin continued to rise 80 minutes after neuropeptide administration. Although there were no increases in the blood levels of melacortin or insulin after the neuropeptides were inhaled, the vasopressin increases were detected in the blood. The scientists propose two ways that neuropeptides may get into the brain: 1. Olfactory neurons capture and "internalize" the peptides. The peptides are then transported inside the neurons to the brain. 2. The neuropeptides pass through small spaces in the olfactory epithelium. The chemicals can then get into areas (subarachnoid space) surrounding the brain. This experiment demonstrates a new way to deliver neuropeptides to the brain. Moreover, because this method allows some neuropeptides to avoid the bloodstream, many potential side effects are eliminated. Intranasal administration of neuropeptides may be a valuable way to treat neurological disorders such as Alzheimer's disease.

References: Born, J., Lange, T., Kern, W., McGregor, G.P., Bickel, U. and Fehm, H.L. Sniffing neuropeptides: a transnasal approach to the human brain. Nature Neuroscience, published online May 6, 2002, DOI: 10.1038/nn849.

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