Triple re-uptake inhibitors for the treatment of depression
Neurons communicate with one another by releasing chemical messengers called neurotransmitters. After release into the synapse (the physical gap that separates two nerve cells), the neuron can take the released neurotransmitter back into the nerve ending (a process called re-uptake). Most of the currently available antidepressants block one or two different types of re-uptake sites. The Richelson laboratory has in development compounds that block re-uptake for 3 different neurotransmitters (norepinephrine, serotonin, and dopamine). These potential antidepressants, which are covered by United States patents, are in the early stages of preclinical testing. In theory, these compounds could be faster acting, as well has be more effective than currently available antidepressant drugs.
A peptide drug for treatment of schizophrenia, Parkinson’s disease, and psychostimulant abuse
Neurons can also communicate with one another by releasing peptides (strings of amino acids bonded together) into the synapse. One such peptide, called neurotensin, has been implicated in the pathophysiology of several neuropsychiatric disorders. In general, peptides do not make good drugs, because they are rapidly broken down by enzyme in the body and have difficulty getting into the brain. The Richelson laboratory has in development some peptide compounds that mimic the effects of neurotensin, but penetrate into brain, after being given outside the brain. Theses compounds, which are also covered by United States patents, are also in the early stages of clinical development. These compounds could be novel treatments for several types of neuropsychiatric diseases.
Peptide nucleic acids as potential antisense and antigene compounds
Peptide or polyamide nucleic acids (PNAs) are DNA analogs that hybridize to complementary nucleic sequences with high affinity and stability. PNAs belong to a group of disease-fighting compounds called “antigene” and ”antisense” agents. Antisense agents interfere with a cell’s ability to make a specific protein by blocking the genetic code that directs the protein’s formation. PNAs mimic many of the structural aspects of the body’s natural DNA, but they are made differently. Composed of the individual bases that make up DNA, they are linked together by bonds that are found in peptides or proteins. PNAs are more resistant to enzymatic degradation, provide greater stability, offer greater affinity for target molecules, and are more easily modified when compared to either natural DNA or first-generation antisense compounds. Research from the Richelson laboratory was the first direct in vivo animal work to demonstrate the biological effects of PNAs. While PNAs were discovered elsewhere, our studies established, among other things, that PNAs could cross both the cell membrane and the blood-brain barrier. We also demonstrated the ability of a PNA sequence to cause antisense effects through systemic administration. For this work, we have been issued U.S. Patents. These compounds, too, are in the early stages of preclinical development.
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