Background:

IC50: 220 and 310 nM for human PLD1 and PLD2, respectively

Halopemide is a phospholipase D (PLD) inhibitor.

Phospholipase D (PLD) is a key enzyme for the production of phosphatidic acid, a lipid second messenger. Phosphatidic acid involves in both G protein-coupled receptor and receptor tyrosine kinase signal transduction networks.

In vitro: In a previous study, the IC50 of halopemide against PLD2 was found to be similar to that previously reported, but the compound had no preference for PLD2 over PLD1 [1].

In vivo: Animal study showed that the halopemide concentration in the rat brain was 10 times less than that of R29800, its chemical analog. However, the levels were the same in the pituitary gland. The highest level of halopemide was found to be in septal and thalamic areas while the neuroleptics were concentrated in the caudate nucleus. Moreover, in the caudate nucleus, halopemide was far less particle-bound [2].

Clinical trial: The activating and resocializing properties of halopemide were evaluating in an open and double-blind study in patients with various psychiatric disorders. The results showed a significant improvement in contact and activity, regardless of the nosological characteristics. Moreover, no significant difference in therapeutic effect between the single and the double dose was found [3].

参考文献:
[1] Scott, S. A.,Selvy, P.E.,Buck, J.R., et al. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nature Chemical Biology 5(2), 108-117 (2009).
[2] Loonen AJ, van Wijngaarden I, Janssen PA, Soudijn W.  Regional localization of halopemide, a new psychotropic agent, in the rat brain. Eur J Pharmacol. 1978 Aug 15;50(4):403-8.
[3] De Cuyper H, van Praag HM, Verstraeten D. The clinical significance of halopemide, a dopamine-blocker related to the butyrophenones. Neuropsychobiology. 1984;12(4):211-6.