Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic.
OBJECTIVE
A tri-substituted benzoflavone moiety (BZF) recently isolated from the methanol extract of aerial parts of the plant Passiflora incarnata Linneaus had exhibited encouraging results in countering the dependence produced by addiction-prone substances like morphine, nicotine, cannabinoids and ethyl alcohol, during the studies performed by the authors. Since the BZF moiety had exhibited significant anxiolytic properties at 10 mg/kg p.o. dose in mice, therefore, it was desirable to evaluate this potential phyto-moiety (BZF) for its own dependence-liabilities It was also deemed viable to evaluate BZF moiety for its possible usefulness in countering the dependence-liabilities associated with the chronic use of benzodiazepines keeping in light their tremendous clinical use in the management of anxiety and insomnia.


METHODS
Different groups of mice were administered BZF alone (10, 50 or 100 mg/kg, p.o.), and concomitantly with diazepam (20 mg/kg, p.o.) in a 21-days treatment regimen, followed by no treatments for the next 72-hours. The withdrawal effects in the form of ambulatory behavior of the treated animals were recorded on the 25th day using an Actophotometer.


RESULTS
The BZF-alone (three doses) treated mice exhibited a normal ambulatory behavior on 25th day. Mice groups receiving co-treatments, i.e., BZF-diazepam concomitantly, also exhibited a normal ambulatory behavior in a dose-dependent manner, i.e., the higher dose of BZF (100 mg/kg) being more effective in countering the withdrawal effects of chronically administered diazepam than the lower doses (10 or 50 mg/kg).


CONCLUSIONS
The studies revealed that the chronic administration of the BZF moiety (three doses), did not exhibit any dependence-liability of its own, even upon an abrupt cessation. Additionally, the BZF co-treatments with diazepam also prevented the incurrence of diazepam-dependence, which might be because of the aromatase enzyme inhibiting properties associated with the BZF moiety.
Dhawan
Kamaldeep
K
Department of Drugs Control, Government of Haryana, Panchkula, India. kdd@glide.net.in
Dhawan
Sanju
S
Chhabra
Sumit
S
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000009:adverse effects*; D003975:Diazepam / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D029598:Passiflora / Q000737:chemistry*; D010936:Plant Extracts / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D019966:Substance-Related Disorders / Q000188:drug therapy*
D014151:Anti-Anxiety Agents; D010936:Plant Extracts; D001569:Benzodiazepines; D003975:Diazepam