Racemic phenibut is a GABAB agonist that possesses anxiolytic and nootropic activity mainly attributed to its R-enantiomer [1]. It is structurally similar to baclofen but differs by the presence of one chlorine atom in the benzene ring and is 30 times less active as a GABAB agonist [2]. Other pharmacological activity includes decreasing the activity of voltage-dependent Ca2+ ionic channels similarly to gabapentin and possibly GABAA agonism at high doses [1,2]. Limited information is available on the pharmacokinetics of phenibut. After systemic absorption, phenibut is rapidly distributed to the brain, kidneys, liver, and urine. The elimination half life is 5.3 hours and 65% of the parent drug is excreted into the urine [1,2].

All published acute toxicities from phenibut are summarized in Table 1 [3-9]. Oral administration of phenibut was the most common route with doses ranging from 1 gram to 30 grams with single oral administration. The onset of desired effects was reported to occur within 2-4 hours following oral ingestion with an overall duration of 7-24 hours. Most patients presented with altered mental status, low levels of consciousness, and agitation upon arousal. In cases characterized by severe agitation, benzodiazepines and antipsychotics demonstrated minimal to moderate effects. All patients were carefully monitored in either an emergency observation or intensive care unit and most were discharged within 24-48 hours from admission.

In contrast to previously reported cases, our patient was also taking fasoracetam which stimulates metabotropic glutamate receptors, up-regulates GABAB receptors, and stimulates the release of acetylcholine from central cholinergic neurons [10]. It is absorbed rapidly after oral administration and has a bioavailability of 79%-97%. The elimination half-life ranges from 4-6.5 hours and is predominately excreted in the urine as unchanged drug [10]. Fasoracetam (NFC-1) has recently obtained an Investigational New Drug (IND) from the Food and Drug Administration to be evaluated in patients with ADHD who have rare glutamate gene mutation and has a well-established safety profile from previous clinical trials at recommended doses (50-800mg a day in divided doses) [10]. The most commonly reported side effects include headache and fatigue. Nevertheless, large doses of fasoracetam could potentially explain the bradycardia experienced by this patient as it is not seen with the reported cases of phenibut overdoses. In addition, fasoracetam could potentially enhance the response to phenibut through the up-regulation of GABAB receptors and decrease the threshold for tolerance that is commonly observed with phenibut.

Phenibut and fasoracetam are widely available from internet sites that are mainly based in the UK and USA [2,8]. These unregulated products place the general public at risk from overdoses and can produce unique toxidromes especially with co-administration of multiple supplements. The clinical management is primarily supportive, but should incorporate a thorough history of recent medication use, including dietary supplements and vitamins. In the majority of phenibut overdoses, the toxicological properties predominantly effects the central nervous system and to a lesser extent the cardiovascular system. Healthcare providers should be prepared to manage or inform patients about the acute excess or withdrawal side effects after phenibut or fasoracetam overdoses [11].