Effect of flupenthixol on subjective and cardiovascular responses to intravenous cocaine in humans

The effects of oral flupenthixol and intramuscular (i.m.) flupenthixol deca noate in combination with intravenous (i.v.) cocaine were evaluated in male cocaine abusers. Participants resided at an inpatient research unit for 27 days followed by an 11-day outpatient period. Oral flupenthixol (2.5 or 5. 0 mg; p.o.) followed by flupenthixol decanoate (10 or 20 mg; i.m.) and plac ebo were investigated in individuals who were randomly assigned to one of t hree groups under double-blind conditions (placebo, low or high dose flupen thixol). During the inpatient period, participants had four fixed cocaine d osing sessions; each session they were administered four doses of i.v. coca ine (approx. 48 mg/70 kg), spaced 14 min apart. These sessions occurred onc e before medication (baseline phase), once following oral medication (oral phase), and twice following intramuscular medication (IM phase). Out of 23 participants, 18 completed the study; 4 of the 5 non-completers were in the high dose flupenthixol group. Overall, there were few subjective, cardiova scular, or cocaine pharmacokinetic differences between the placebo group an d the low dose flupenthixol group, indicating that the low dose of flupenth ixol was well tolerated, but ineffective. In the high dose flupenthixol gro up, two out of seven individuals (29%) experienced a dystonic reaction foll owing oral flupenthixol and were medically discharged. Taken together, thes e findings indicate that flupenthixol is not a good candidate for treating cocaine abusers. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .