Prochlorperazine-d8 (hydrochloride)

Prochlorperazine-d₈ is intended for use as an internal standard for the quantification of prochlorperazine by GC- or LC-MS. Prochlorperazine is a dopamine D₂ receptor antagonist with K_i values of 4.7 and 2.9 nM for rat recombinant D₂ receptors in CHO cells and rat striatal membranes, respectively.^1,2 It also binds to rat recombinant D₃ receptors expressed in CHO cells (K_i = 35 nM) and to the serotonin (5-HT) receptor subtype 5-HT₃ in N1E-115 mouse neuroblastoma cell membranes (K_i = 1,200 nM).^1,3 Prochlorperazine (2 mg/kg) increases the latency to paw licking in a hot plate test, indicating analgesia, an effect that is blocked by antisense oligonucleotides against the M₁ muscarinic receptor.⁴ It also inhibits emesis induced by apomorphine in dogs (ED₅₀ = 0.34 mg/kg).⁵ Formulations containing prochlorperazine have been used in the treatment of psychotic disorders and as antiemetics.

1.Sokoloff, P., Giros, B., Martres, M.P., et al.Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neurolepticsNature137(6289)146-151(1990) 2.Tsuchihashi, H., Sasaki, T., Kojima, S., et al.Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatumJ. Pharm. Pharmacol.44(11)911-914(1992) 3.Lummis, S.C., and Baker, J.Radioligand binding and photoaffinity labelling studies show a direct interaction of phenothiazines at 5-HT3 receptorsNeuropharmacology36(4-5)665-670(1997) 4.Ghelardini, C., Galeotti, N., Uslenghi, C., et al.Prochlorperazine induces central antinociception mediated by the muscarinic systemPharmacol. Res.50(3)351-358(2004) 5.Niemegeers, C.J.E.Antiemetic specificity of dopamine antagonistsPsychopharmacology (Berl).78(3)210-213(1982)