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Poffenbarger M, Fuller GM.
“Effects of Psychotropic Drugs on Neurotubule Assembly”.
J.Neurochem.. 1977;28(6):1167-74.
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Abstract
The effects of psychotropic drugs on neurotubule assembly were studied. Purified tubulin (TB) was prepared by repeated polymerization and depolymerization of the 100,000 x g supernatant (crude extract) obtained from bovine brain homogenates. The effects of atropine, melatonin (both Sigma), chlorpromazine (CPZ), d-amphetamine (AM), reserpine (R), scopolamine, colchicine (CC; Sigma), phenylethylamine, p-methoxyphenyl ethylamine, mescaline, LSD, norepinephrine, dopamine, phenylalanine, and phenylpyruvic acid on microtubule (MT) re assembly were estimated by monitoring the viscosity of crude extracts when incubated with 1 mM GTP. The presence of MTs was verified electron microscopically The ability of test drugs to inhibit binding of 3H-acetylcolchicine (3H-ACC; NON) to purified TB was determined. The effect of drugs on the development of neurites by neuroblastoma cells (N-18) in serum-free medium was also elucidated. Only CPZ, AM, CC and R exhibited inhibitory effects on MT reassembly; polymerization was inhibited 100% by CC at 1 x 10-5 M, 55.2% by CPZ at 1 x 10-3 M, 31.4% by AM at 5 x 10-3 M, and 22% by R at 1 x 10-6 M. The low aqueous solubility of R prevented further study of its effects in other assay systems. 3H-ACC binding to purified TB was significantly reduced by both CPZ (7570 at 7 x 10-4 M) and AM (67% at 5 x 10-3 M). Furthermore, inhibition of neurite outgrowths from neuroblastoma cells with out apparent cell death was observed following incubations with 1 x 10-4 and 5 x 10-4 M CPZ, 5 x 10-3 M AM, and 1 x 10-6 M CC. The toxicity of certain psychotropic drugs may be mediated partly by an action on the MT assembly system. Their affinity for TB, similar to, although that of CC, may be important in this respect though disruption of secondary assembly processes could be equally significant.
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