Magazine article Clinical Psychiatry News
Drug's Efficacy for Treating Depression 'Exciting'
VIENNA -- Mecamylamine, an old, rarely prescribed, truly obscure antihypertensive agent, may be favorably reincarnated as an antidepressant with a completely novel mechanism of action--and vastly greater potential use.
The drug displayed favorable safety and efficacy as augmentation therapy in a double-blind, placebo-controlled trial in patients with major depressive disorder (MDD) who were nonresponders to citalopram (Celexa) monotherapy, Dr. Geoffrey C. Dunbar reported at the annual congress of the European College of Neuropsychopharmacology.
"This study provides the first substantive clinical evidence that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties," said Dr. Dunbar, vice president for clinical development and regulatory affairs at Targacept Inc., Winston-Salem, N.C.
The mechanism of benefit is the blocking of the central nervous system (CNS) nicotinic receptors, which is thought to restore balance to a deranged cholinergic tone implicated in depression.
"It's really very exciting because there have been no new pharmacologic approaches in depression therapy in 30 years," the psychiatrist said later in an interview.
However, Targacept will move forward with development not of mecamylamine, but of its S-enantiomer, as a treatment for depression. The enantiomer, trade name Amplixa, has gotten the green light from the Food and Drug Administration for accelerated development on the strength of the reassuring safety profile established over many years by its racemic relative, mecamylamine, Dr. Dunbar continued.
Mecamylamine was approved for treatment of hypertension in the mid-1950s but never gained broad use as an antihypertensive agent. Today, mecamylamine sees some off-label use for the behavioral and mood disorders associated with autism and Tourette syndrome, he said.
Mecamylamine is a broad-spectrum nicotinic receptor antagonist, meaning that it blocks receptors located in the periphery of, as well as those in, the CNS. An insight that was key to unlocking its antidepressant potential was the discovery that at dosages of 2. …