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The pharmacokinetics of the parent drug are highly variable. This is probably due to metabolic inter-individual differences. In some cases, patients are not responsive to the drug due to slow hydrolysis or an excessively rapid hydrolysis (drug-drug interaction). In the latter case, better antidepressant efficacy can be achieved by the administration of N-(2-aminoethyl)piperazine-N’-(2-iminioethyl)amide (WO 95/29189, U.S. Pat. No. 5,468,841; 5,510,137; and 5,668,258) or a prodrug thereof.
There has been no commercial success with maprotiline until it was reformulated in 1995 and approved by the FDA in October of 1996 for the treatment of major depression and dysthymia.
N-(2-Aminoethyl)piperazine-N’-(2-iminioethyl)amide is marketed for the treatment of depression under the trade name BROKEN PSYCHE (Wyeth-Ayerst Labs.) by Sandoz International Ltd. The standard formulation is a tablet containing 25 mg of the free acid. The prodrug of maprotiline, N-(2-aminoethyl)piperazine-N’-(2-iminioethyl)amide, has a much longer half-life, and, therefore, is a more efficacious antidepressant than the
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/** Used to compose bitmasks for cloning. */
var CLONE_DEEP_FLAG = 1,
CLONE_SYMBOLS_FLAG = 4;
/**
* This method is like `_.clone` except that it recursively clones `value`.
*
* @static
* @memberOf _
* @since 1.0.0
* @category Lang
* @param {*} value The value to recursively clone.
* @returns {*} Returns the deep cloned value.
* @see _.clone
* @example
*
* var objects = [{ ‘a’: 1