Neuroscience 2000 Abstract
| Presentation Number: | 589.12 |
|---|---|
| Abstract Title: | Lofexidine: an alpha-2 adrenergic agonist for the alleviation of opiate withdrawal. |
| Authors: |
Herman, B. H.*
; Yu, E.
; Miotto, K.
; Li, S. H.
; Martz, K.
; Walsh, R.
; Montgomery, A.
; Chiang, N.
; Poole, S.
; Fudala, P. J.
; Cornish, J. W.
; Whittington, J.
; Davies, K.
; Ling, W.
; Vocci, F.
; O'Brien, C. P.
|
| Primary Theme and Topics |
J. Disorders of the Nervous System and Aging - 146. Drugs of abuse: opioids and others |
| Secondary Theme and Topics | I. Neural Basis of Behavior<br />- 119. Neuropeptides and behavior |
| Session: |
589. Drugs of abuse: nicotine and morphine Slide |
| Presentation Time: | Wednesday, November 8, 2000 10:45 AM-11:00 AM |
| Location: | Room 273 |
| Keywords: | Detoxification, Withdrawl, Blood Pressure, Human |
Alpha-2 adrenergic agonists reduce opiate withdrawal (OW), but a limiting side effect of clonidine (CLON) is significant hypotension. Double-blind controlled investigations indicate that lofexidine (LOF), also an alpha-2 adrenergic agonist, produces significantly less hypotension than CLON, but displays similar efficacy. Our group has reported on a Phase II, 20 day open, two site (Phil, LA), inpatient study assessing the tolerability and preliminary efficacy of LOF (1.6 (n=9), 2.4 (n=9 Phil, n=13 LA), 4.0 (n=3) mg/day), and preliminary results of a shorter duration (11-14 days, pilot I) 3.2 (n=6) mg/day study (n = evaluable subjects) (SFN, Herman et al., 1999). This study was the first to utilize: a dose-response analysis of LOF, LOF doses > 2.6 mg/day, morphine for stabilization, and initial plateau LOF doses, with three phases: morphine stabilization, detoxification/LOF treatment, and no medication. The Phase II investigation is now complete, including results of two 3.2 mg/day studies (pilot I below). No serious adverse events were observed. One subject displayed syncope at LA (transient at 2.4 mg/day). The subject incidence of dizziness (1 event) during the LOF period was: 1.6 mg (3/9), 2.4 mg (5/9), 3.2 mg (4/6), 4.0 mg (2/3) in Phil and 2.4 mg (0/13) in LA. Two subjects exhibited vertigo (Phil only) (1.6 mg, 2.4 mg). Overall, there were no clinically significant quantitative decreases in sitting systolic blood pressure (BP) at either 1.6 or 2.4 mg/day at Phil or at 2.4 mg at LA, but such effects were obtained at 3.2 and 4.0 mg/day. There were transient dose-dependent decreases in orthostatic systolic BP (< 85 mmHg) Phil (1.6 (2/9), 2.4 (5/9), 3.2 mg (4/6), 4.0 (3/3) mg/day dose (subjects). There were log dose-dependent decreases in objective OW symptoms (3.2 mg similar to 4.0 mg). Doses ≥ 3.2 mg abolished OW-induced emesis. Overall, these results suggest that the optimal tolerable/ maximally efficacious dose of LOF for OW is 3.2 mg/day.
Supported by <I>IAG between DTRD, NIDA and Phil and Long Beach, VA & a CTA between NIDA and Britannia Pharmaceuticals.</I>
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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