The binding of amphiphilic amines to phospholipids was investigated. Dopamine (51616), phenylpropanolamine (492411), ephedrine (299423), phentermine (122098), or chlorphentermine (461789) at concentrations of 0 to 10(-2) molar (M) was incubated with dispersions containing 5x10(-8) to 5x10(-6)M 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), phosphatidylserine, or 1,2-dipalmitoyl-sn-glycero-3- phosphoglycerol. The extent of amine/phospholipid binding was determined using spectrofluorometry utilizing 1-anilino-8- naphthalene-sulfonate, ammonium-salt (ANS) and 1,6-diphenyl-1,3,5- hexatriene (DPH) as fluorescence probes. Phenylpropanolamine, ephedrine, phentermine, and chlorphentermine enhanced the intensity of the ANS probe when incubated with DPPC. Chlorphentermine, but not the other amines, quenched the fluorescence of phospholipid bound DPH. Chlorphentermine showed the greatest affinity for DPPC, followed by phentermine, ephedrine, and phenylpropanolamine in that order. Dopamine did not show any phospholipid interaction. Additionally, 0.25 micrograms per milliliter phospholipase-A2 (PA2) was incubated with 1x10(-5)M DPPC, 0 or 6x10(-3) calcium ion (Ca+2), and 0 or 6x10(-3)M chlorphentermine for 9 minutes and the effects on PA2 catalyzed hydrolysis of DPPC were monitored utilizing the ANS probe. No hydrolysis occurred when Ca+2 was absent. In the absence of chlorphentermine, the rate of DPPC hydrolysis increased rapidly and plateaued after 3 to 5 minutes. Chlorphentermine decreased the extent of DPPC hydrolysis (after plateauing) but not the initial rate. The authors conclude that phospholipids bind to cationic amphiphilic amines as a result of ionic and hydrophobic interactions. Amines such as dopamine that do not have a strong nonpolar moiety do not interact with phospholipids. Strong amphiphilic amines such as chlorphentermine can inhibit metal ion activated enzymatic degradation of phospholipids. This inhibition may be an important factor in drug induced lipidosis.