zolpidem , a nonbenzodiazepine hypnotic which binds to the benzodiazepine binding site on the gamma - aminobutyric acid type a ( gaba - a ) receptors , was introduced in europe in 1986 , then in france in 1987 ( stilnox ) and in united stated of america ( usa ) in 1993 for treatment of insomnia .
metabolism of zolpidem mediated by human cytochromes p450 ( cyp ) ; so that cyp3a4 has a dominant role and cyp2c9 , 1a2 , 2d6 , and 2c19 have a contributory role in decreasing order of importance ; but cyp 2a6 , 2e1 , or 2c8 have no role in zolpidem metabolism .
zolpidem has a sedation property without interfering with other benzodiazepine properties linked to other receptor subtypes .
zolpidem has no residual effects and this may be due to its rapid metabolism via cyp3a4 and cyp1a2 isoenzymes and a short elimination half - life .
several studies have reported efficacy and safety of zolpidem , its well - tolerance in adults and elderly during administration and minimal risk of abuse or dependence.[23461011 ] interestingly , in this case , zolpidem induced euphoric state and gradually cause tolerance , withdrawal syndrome , and led to dose increase .
the patient was 32-year - old jeweler man who had diploma degree was referred to psychiatric clinic because of restlessness , irritability , myalgia , muscle cramps , sweating , palpitation , insomnia , muscle tic , and jump due to withdrawal of daily use of 400 mg zolpidem .
he started to use heroin recreationally since 1997 and after 1 year had used it daily in snuff route for 3 years .
then , he was introduced to narcotics anonymous ( na ) and was abstinent for 6 years .
two years ago , he used orap ( pimozide ) and xanax ( alprazolam ) to treat tic and simultaneous anxiety , but he discontinued xanax because of failure to reduce anxiety and insomnia and his physician prescribed 10 mg tablet of zolpidem instead of xanax .
after use of first dose of zolpidem , he experienced euphoric mood of his heroin addiction and reminded heroin use .
the next day , to avoid experience of heroin dependency and its induced euphoria , he used 40 tablets of diphenoxylate with zolpidem , but gradually increased dose of zolpidem and diphenoxylate simultaneously so that he used 100 tablets of zolpidem and 120 tablets of diphenoxylate within 6 months .
then , 6 months later , he discontinued diphenoxylate and used 110 - 140 10 mg tablets of zolpidem ( 1,100 - 1,400 mg ) until he experienced convulsion with use of 200 10 mg tablets of zolpidem and hospitalized , and after discharge zolpidem was discontinued completely for 1 month but prescribed zolpidem 10 mg / day again after 1 month .
tics were treated completely with zolpidem use but its dosage increased to 1,000 mg / day again and within 6 months decreased to 400 mg / day and discontinued completely a few days before attending psychiatric clinic and he had classic symptoms and signs of opioid withdrawal ( runny nose , diarrhea , myalgia , irritability , insomnia , and  ) .
he had no history of physical problems and known diseases and only had a history of tic in past psychiatric history .
benzodiazepines exert their effects through three subtypes of gaba - a receptors . binding to omega 1 ( 1 ) subtype has hypnotic and anxiolytic effects and binding to omega 2 ( 2 ) receptor has anxiolytic , myorelaxant , respiratory depression , psychomotor dysfunction effects , and anticonvulsant property .
omega 3 ( 3 ) subtype has different structure and function and are on glial cells and other cells .
zolpidem as an imidazopyridine is not considered a classic benzodiazepine because of lack of diazepine cycle in chemical structure , but its clinical effect is through benzodiazepine receptors and its effect could be blocked by benzodiazepine antagonists such as flumazenil.[178 ] it has been reported that zolpidem has low abuse and dependency capability ; however , many cases of zolpidem abuse and dependency were reported in various european countries and usa.[2368910111213 ] this case showed that zolpidem can exert abuse and dependency capability and in this case it may be through nonbenzodiazepine receptors because with first dose of zolpidem , the patient experienced euphoric mood ; and interestingly , he discontinued a potent benzodiazepine such as alprazolam due to lack of euphoria and sedation and used zolpidem instead of it and increased zolpidem dose gradually . after a while ,
according to the patient , he had reminded euphoric mood due to heroin in first use of zolpidem .
thus , despite primary reports of zolpidem safety and minor abuse and dependency capability , recent reports especially this case showed that zolpidem can exert abuse and dependency .
it has been reported that zolpidem pharmacodynamics and pharmacokinetics may have a crucial role in cases of zolpidem abuse , dependence , and withdrawal syndrome .
it is suggested that zolpidem might lose its selectivity on gaba - a receptor and exert the same pharmacological effects as classical benzodiazepines .
also , low zolpidem clearance capacity in elderly and female population might predispose patients to zolpidem dependence .
it has been proposed that possible gaba - a receptor mutations may be a predisposing factor in zolpidem dependency .
 zolpidem , a nonbenzodiazepine hypnotic , binds to the benzodiazepine binding site on the gamma - aminobutyric acid type a ( gaba - a ) receptors . 
 many studies have reported efficacy and safety of zolpidem in treatment of insomnia , low abuse , and dependence capability . 
 however , many cases of zolpidem abuse and dependence were reported around the world . 
 this case showed that zolpidem can exert abuse capability , euphoric mood , tolerance , and withdrawal syndrome . 
INTRODUCTION
CASE REPORT
DISCUSSION