Scientific Rationale
Psychiatric diseases including ADHD and depression have been associated with impaired neurotransmission of the serotonin, norepinephrine, and dopamine pathways. However, most pharmacologic treatments aim to enhance only serotonin and/or norepinephrine. Many patients do not adequately respond to these products, are dissatisfied with their side effects, or feel they respond too slowly.
Prexas research is focused on a new class of monoamine inhibitors which inhibit the reuptake of all three neurotransmitters, but with greatest potency on the dopamine transporter. No other agents in development offer this order of potency. We believe a dopamine-preferring triple reuptake inhibitor (TRI) has potential clinical utility in a range of psychiatric and neurologic indications including ADHD, major depressive disorder, Parkinsons disease, pain syndromes such as neuropathic pain, and addictive disorders.
ADHD
Adults and children with ADHD are often treated with stimulants that carry significant abuse liability, or with other agents that are slow-acting and often not fully effective. A drug that safely enhances both dopamine and norepinephrine, through mechanisms less likely to cause abuse liability, may offer a significant advance in the treatment of this disorder.
Depression
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, or serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, were designed to be as effective as the oldest class of antidepressant drugs, tricyclics, but without the side effects attributable to anticholinergic and other off-target actions. Given their increased selectivity, SSRIs and SNRIs have shown better tolerability and reduced adverse events relative to the tricyclics and monoamine oxidase inhibitors, but efficacy is still lacking for many patients. Triple reuptake inhibitors may improve the efficacy of these agents while avoiding the side effects of older classes of drugs.
Parkinsons Disease
New treatments for Parkinsons disease have provided modest benefits when added to levodopa/carbidopa, but the need remains for new agents that can improve symptoms when given either as monotherapy or in conjunction with L-DOPA preparations. Dopamine reuptake inhibitors, as well as dual inhibitors of dopamine and norepinephrine, provide a rational new approach to this debilitating condition.