11

ADHD: Non-Stimulant drugsADHD: Non-Stimulant drugs

Or Other drugsOr Other drugs

Or Second-line drugsOr Second-line drugs

MRMMRM

33

دكتر محمد رضا محمدي

روانپزشكي كودك و نوجوان روانپزشكي كودك و نوجوانفوق تخصصفوق تخصص

و و روانپزشكيروانپزشكياستاد استاد تحقيقات مركز تحقيقات رئيس مركز و رئيس و روانپزشکی روانپزشکی

روانشناسیروانشناسی

پزشكي علوم پزشكي دانشگاه علوم تهران تهران دانشگاهبيمارستان روزبهبيمارستان روزبه

Email: Email: mohammadimr@tums.ac.ir

44

اختالل نقص توجه و بيش فعالياختالل نقص توجه و بيش فعالي تعريفتعريف

DSM – IV-TRDSM – IV-TR بر اساسبر اساس

Attention Deficit Hyperactivity Disorder

(ADHD)

نقص نقص و ونارس0ایینارس0اییعب0ارت اس0ت از ي0ك الگ0وي مق0اوم عب0ارت اس0ت از ي0ك الگ0وي مق0اوم

فع0الي ك0ه ب0ا تك0رار و ش0دت بيش0تر از فع0الي ك0ه ب0ا تك0رار و ش0دت بيش0تر از توج0ه و بيشتوج0ه و بيش

كودك0ان س0الم و مش0ابه از لح0اظ س0ن و جنس ب0روز كودك0ان س0الم و مش0ابه از لح0اظ س0ن و جنس ب0روز

.مينمايدمينمايد

55

ADHD is definedADHD is defined InattentivenessInattentiveness

• disorganised, forgetful, does not invest disorganised, forgetful, does not invest

effort effort

• brief and changing activitiesbrief and changing activities

HyperactivityHyperactivity

• depending on contextdepending on context

Impulsiveness Impulsiveness

• action without reflectionaction without reflection

66

Prevalence of disorderPrevalence of disorder IRAN

Tehran: 3%-5%Tehran: 3%-5% Children 8.6 % –Adolescent 8.3 %Children 8.6 % –Adolescent 8.3 %

Khorramabad: 3%-6%Khorramabad: 3%-6%

Other Studies: 2 % -20 %Other Studies: 2 % -20 %

77

Principles of psychological treatmentPrinciples of psychological treatmentPrinciples of psychological treatmentPrinciples of psychological treatment

Identify specific problemsIdentify specific problems Analyze contingencies (events)Analyze contingencies (events) Enhance adult attending Enhance adult attending Teach effective instructionTeach effective instruction Token economy Token economy Time-out + rapid novel rewardsTime-out + rapid novel rewards Self- managementSelf- management

88

Interventions in the classroomInterventions in the classroomInterventions in the classroomInterventions in the classroom

Proximity to teacherProximity to teacher

Managed transitionsManaged transitions

Letting off energyLetting off energy

Classroom aideClassroom aide

• operant conditioningoperant conditioning

• peer advicepeer advice

Rule governmentRule government

Clarity of goal Clarity of goal

speed of feedbackspeed of feedback

99

TreatmentsTreatments EducationEducation

Cognitive-Behavior therapyCognitive-Behavior therapy

School modificationSchool modification

Triple P: Positive Parents ProgramTriple P: Positive Parents Program

PsychopharmacologyPsychopharmacology

Stimulant drugsStimulant drugs

Other drugsOther drugs

Non-Stimulant drugsNon-Stimulant drugs

Or Second-line drugsOr Second-line drugs

1010

Medication typesMedication typesMedication typesMedication types

Stimulant drugs:

Methylphenidate Methylphenidate

DexamphetamineDexamphetamine

Adderall Adderall

Extended-release MPExtended-release MP

1111

Why is Methylphenidate (Ritalin) effective in ADHD?

Its mechanism(s) of action are not understood

•Most commonly prescribed psychoactive drug in children.

• In the USA, 4-6 million children are treated with methylphenidate every day.

•Has been used for over 40 years for ADHD.

1212

Why stimulants failWhy stimulants fail They are not being takenThey are not being taken

Extended release; education; motivationalExtended release; education; motivational

The dose is wrongThe dose is wrongMonitor dose range to High dose; distribute; second Monitor dose range to High dose; distribute; second

stimstimtt..

Adverse effects limit Adverse effects limit benefit Manage symptomatically; modify dosebenefit Manage symptomatically; modify dose

The diagnosis is wrongThe diagnosis is wrong

The disorder is refractoryThe disorder is refractorySecond-line drugs; CBT approachesSecond-line drugs; CBT approaches

1313

:شايع

كاهش   - 1

اشتها

كاهش وزن     -2

بدن

عصبانيت و   -3

پرخاشگري

اشكال در به    -4

خواب رفتن

وارض جانبي ريتالينعتربا يوع كم ردرد، -: ش س

^وع ، درد ^رگيجه ، ته^ س^

مع^ده ، اف^زايش ض^ربان

قلب.

درد قفس^ه س^ينه ، درد -

^ير ^ات غ ^ل ، حرك مفاص

ارادي بدن.

  بثورات پوستي ، كهير -

، اكيموز

^ل - ^ ^ ^دون دلي ^ ^    تب ب

شناخته شده

ت^اري دي^د ، تش^نج ، :ادرن

تغ^^^^يرات خلقي ، گل^^^^و

درد ، پسيكوز

1414

SSRIs

FluoxetineFluoxetine

CitaloprameCitaloprame

sertralinesertraline

1515

Trial evidence AtomoxetineAtomoxetine Haloperidol Haloperidol ImipramineImipramine Clonidine Clonidine Bupropion Bupropion PemolinePemoline Nicotine Nicotine CarbamazepineCarbamazepine

1616

Few Trial

GuanfacineGuanfacine

Moclobemide (MAoI)Moclobemide (MAoI)

VenlafaxineVenlafaxine

RisperidoneRisperidone

1717

AntidepressantsAntidepressants Imipramine Imipramine 20-100 mg20-100 mg Amitriptyline Amitriptyline 20-100 mg20-100 mg DesipramineDesipramine 20-100 mg20-100 mg NortriptilineNortriptiline 10-50 10-50

BupropionBupropion 75-30075-300

ClomipramineClomipramine 25-10025-100

TranylcipromineTranylcipromine 5-155-15 ClorgylineClorgyline 5-205-20 PargylinePargyline

1818

αα22-Agonists-Agonists

GuanfacineGuanfacine 0.5-4.00.5-4.0

ClonidineClonidine 0.05-0.30.05-0.3

1919

miscellaneousmiscellaneous

BuspironeBuspirone 5-305-30

DiphenhydramineDiphenhydramine75-15075-150

Nicotine (only adult) 7-21 Nicotine (only adult) 7-21 mg patchmg patch

ModafinilModafinil 100-400 mg100-400 mg

2020

Anticonvulsants

CarbamazepineCarbamazepine 50-800 50-800 (serum level)(serum level)

ValproateValproate 50-600 50-600 (serum level)(serum level)

PhenytoinPhenytoin 50-30050-300

2121

Antipsychotics

ThioridazineThioridazine 25-15025-150

HalopridolHalopridol 0.5-50.5-5

ChlorpromazineChlorpromazine 25-15025-150

RisperidoneRisperidone 0.25-20.25-2

2222

Precursors

Tryptophan (Tryptophan (precursor of serotoninprecursor of serotonin) ) 70-10070-100

Tyrosine Tyrosine ((precursor of dopamine & norepinephrineprecursor of dopamine & norepinephrine) ) 100-400 100-400

Phenyalanine (Phenyalanine (precursor of dopamine & precursor of dopamine &

norepinephrinenorepinephrine)) 100-400100-400

Levo-DOPA (Levo-DOPA (precursor of dopamine & precursor of dopamine &

norepinephrinenorepinephrine)) Deanol (Deanol (precursor of acetylcholineprecursor of acetylcholine) ) >500>500

2323

Others

ββ Blockers Blockers

PropranololPropranolol 10-10010-100

CaffeineCaffeine 100-450100-450

2424

Clinical Trial in Iran TheophillineTheophilline 3/4 mg/kg/day

Ritalin + ZNRitalin + ZN 55 mg/day 55 mg/day

SelegilineSelegiline 5-10 mg5-10 mg

PasipayPasipay 0.04 0.04 mg/kg/day

Modafinil Modafinil 100-400 mg100-400 mg

2525

Clinical Trial in Iran

Ginkgo BilobaGinkgo Biloba 240-600mg240-600mg

BuspironeBuspirone 5-10 mg5-10 mg

BupropionBupropion 37.5-150 mg37.5-150 mg

1- Mohammadi, M.R., Ghanizadeh, A., Alaghband-rad, J., Tehranidoost, M., Mesgarpour, B., Soori, H.Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial(2004) Journal of Child and Adolescent Psychopharmacology, 14 (3), pp. 418-425. Cited 16 times.

2- Mohammadi, M.R., Kashani, L., Akhondzadeh, S., Izadian, E.S., Ohadinia, S.Efficacy of Theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: A pilot double-blind randomized trial(2004) Journal of Clinical Pharmacy and Therapeutics, 29 (2), pp. 139-144. Cited 16 times.

2626

3- Mohammadi, M.R., Mostafavi, S.A., Keshavarz, S.A., 3- Mohammadi, M.R., Mostafavi, S.A., Keshavarz, S.A., Eshraghian, M.R., Hosseinzadeh, P., Hosseinzadeh-Eshraghian, M.R., Hosseinzadeh, P., Hosseinzadeh-Attar, M.J., Kooshesh, S.M.A., Chamari, M., Attar, M.J., Kooshesh, S.M.A., Chamari, M., Akhondzadeh, S.Akhondzadeh, S.MelatoninMelatonin effects in methylphenidate treated effects in methylphenidate treated children with attention deficit hyperactivity children with attention deficit hyperactivity disorder: A randomized double blind clinical trialdisorder: A randomized double blind clinical trial(2012) (2012) Iranian Journal of PsychiatryIranian Journal of Psychiatry, 7 (2), pp. 87-, 7 (2), pp. 87-92. Cited 2 times.92. Cited 2 times.

4- Mohammadi, M.-R., Hafezi, P., Galeiha, A., 4- Mohammadi, M.-R., Hafezi, P., Galeiha, A., Hajiaghaee, R., Akhondzadeh, S.Hajiaghaee, R., Akhondzadeh, S.BuspironeBuspirone versus methylphenidate in the versus methylphenidate in the treatment of children with attention- deficit/ treatment of children with attention- deficit/ hyperactivity disorder: Randomized double-blind hyperactivity disorder: Randomized double-blind studystudy(2012) (2012) Acta Medica IranicaActa Medica Iranica, 50 (11), pp. 723-728. Cited , 50 (11), pp. 723-728. Cited 1 time.1 time.

5- Mohammadi, M.-R., Kazemi, M.-R., Zia, E., Rezazadeh, S.-5- Mohammadi, M.-R., Kazemi, M.-R., Zia, E., Rezazadeh, S.-A., Tabrizi, M., Akhondzadeh, S.A., Tabrizi, M., Akhondzadeh, S.AmantadineAmantadine versus methylphenidate in children and versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: adolescents with attention deficit/hyperactivity disorder: A randomized, double-blind trialA randomized, double-blind trial(2010) (2010) Human PsychopharmacologyHuman Psychopharmacology, 25 (7-8), pp. 560-, 25 (7-8), pp. 560-565. Cited 9 times.565. Cited 9 times.

6- Mostafavi, S.A., Mohammadi, M.R., Hosseinzadeh, P., 6- Mostafavi, S.A., Mohammadi, M.R., Hosseinzadeh, P., Eshraghian, M.R., Akhondzadeh, S., Hosseinzadeh-Attar, Eshraghian, M.R., Akhondzadeh, S., Hosseinzadeh-Attar, M.J., Ranjbar, E., Kooshesh, S.M.A., Keshavarz, S.A.M.J., Ranjbar, E., Kooshesh, S.M.A., Keshavarz, S.A.Dietary intake, growth and development of children Dietary intake, growth and development of children with ADHD in a randomized clinical trial of ritalin and with ADHD in a randomized clinical trial of ritalin and melatoninmelatonin co-administration: Through circadian cycle co-administration: Through circadian cycle modification or appetite enhancement?modification or appetite enhancement?(2012) (2012) Iranian Journal of PsychiatryIranian Journal of Psychiatry, 7 (3), pp. 114-119. , 7 (3), pp. 114-119. 

7- Akhondzadeh, S., Mohammadi, M.-R., Khademi, M.7- Akhondzadeh, S., Mohammadi, M.-R., Khademi, M.Zinc sulfate Zinc sulfate as an adjunct to methylphenidate for the as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial children: A double blind and randomized trial [ISRCTN64132371][ISRCTN64132371](2004) (2004) BMC PsychiatryBMC Psychiatry, 4, art. no. 9, . Cited 69 times., 4, art. no. 9, . Cited 69 times.

8- Kahbazi, M., Ghoreishi, A., Rahiminejad, F., Mohammadi, 8- Kahbazi, M., Ghoreishi, A., Rahiminejad, F., Mohammadi, M.-R., Kamalipour, A., Akhondzadeh, S.M.-R., Kamalipour, A., Akhondzadeh, S.A randomized, double-blind and placebo-controlled trial A randomized, double-blind and placebo-controlled trial of of modafinil modafinil in children and adolescents with attention in children and adolescents with attention deficit and hyperactivity disorderdeficit and hyperactivity disorder(2009) (2009) Psychiatry ResearchPsychiatry Research, 168 (3), pp. 234-237. Cited 39 , 168 (3), pp. 234-237. Cited 39 times.times.

9- Amiri, S., Mohammadi, M.-R., Mohammadi, M., 9- Amiri, S., Mohammadi, M.-R., Mohammadi, M., Nouroozinejad, G.-H., Kahbazi, M., Akhondzadeh, S.Nouroozinejad, G.-H., Kahbazi, M., Akhondzadeh, S.ModafinilModafinil as a treatment for as a treatment for Attention-Deficit/Hyperactivity Disorder in children Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind, randomized and adolescents: A double blind, randomized clinical trialclinical trial(2008) (2008) Progress in Neuro-Psychopharmacology and Progress in Neuro-Psychopharmacology and Biological PsychiatryBiological Psychiatry, 32 (1), pp. 145-149. Cited 37 times., 32 (1), pp. 145-149. Cited 37 times.

10- Salehi, B., Imani, R., Mohammadi, M.R., Fallah, J., 10- Salehi, B., Imani, R., Mohammadi, M.R., Fallah, J., Mohammadi, M., Ghanizadeh, A., Tasviechi, A.A., Mohammadi, M., Ghanizadeh, A., Tasviechi, A.A., Vossoughi, A., Rezazadeh, S.-A., Akhondzadeh, S.Vossoughi, A., Rezazadeh, S.-A., Akhondzadeh, S.Ginkgo biloba Ginkgo biloba for Attention-Deficit/Hyperactivity for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double Disorder in children and adolescents: A double blind, randomized controlled trialblind, randomized controlled trial(2010) (2010) Progress in Neuro-Psychopharmacology and Progress in Neuro-Psychopharmacology and Biological PsychiatryBiological Psychiatry, 34 (1), pp. 76-80. Cited 24 times., 34 (1), pp. 76-80. Cited 24 times.

11- Zarinara, A.-R., Mohammadi, M.-R., Hazrati, N., 11- Zarinara, A.-R., Mohammadi, M.-R., Hazrati, N., Tabrizi, M., Rezazadeh, S.-A., Rezaie, F., Akhondzadeh, Tabrizi, M., Rezazadeh, S.-A., Rezaie, F., Akhondzadeh, S.S.VenlafaxineVenlafaxine versus methylphenidate in pediatric versus methylphenidate in pediatric outpatients with attention deficit hyperactivity outpatients with attention deficit hyperactivity disorder: A randomized, double-blind disorder: A randomized, double-blind comparison trialcomparison trial(2010) (2010) Human PsychopharmacologyHuman Psychopharmacology, 25 (7-8), pp. 530-, 25 (7-8), pp. 530-535. Cited 14 times.535. Cited 14 times.

  12- Akhondzadeh, S., Mohammadi, M.R., Momeni, F.12- Akhondzadeh, S., Mohammadi, M.R., Momeni, F.Passiflora Passiflora incarnata in the treatment of incarnata in the treatment of attention-deficit hyperactivity disorder in attention-deficit hyperactivity disorder in children and adolescentschildren and adolescents(2005) (2005) TherapyTherapy, 2 (4), pp. 609-614. Cited 14 times., 2 (4), pp. 609-614. Cited 14 times.

13- Abbasi, S.-H., Heidari, S., Mohammadi, M.-R., Tabrizi, M., 13- Abbasi, S.-H., Heidari, S., Mohammadi, M.-R., Tabrizi, M., Ghaleiha, A., Akhondzadeh, S.Ghaleiha, A., Akhondzadeh, S.Acetyl-L-carnitineAcetyl-L-carnitine as an adjunctive therapy in the as an adjunctive therapy in the treatment of attention-deficit/hyperactivity disorder treatment of attention-deficit/hyperactivity disorder in children and adolescents: A placebo-controlled in children and adolescents: A placebo-controlled trialtrial(2011) (2011) Child Psychiatry and Human Child Psychiatry and Human DevelopmentDevelopment, 42 (3), pp. 367-375. Cited 6 times., 42 (3), pp. 367-375. Cited 6 times.

14- Jafarinia, M., Mohammadi, M.-R., Modabbernia, A., 14- Jafarinia, M., Mohammadi, M.-R., Modabbernia, A., Ashrafi, M., Khajavi, D., Tabrizi, M., Yadegari, N., Ashrafi, M., Khajavi, D., Tabrizi, M., Yadegari, N., Akhondzadeh, S.Akhondzadeh, S.BupropionBupropion versus methylphenidate in the treatment versus methylphenidate in the treatment of children with attention-deficit/hyperactivity of children with attention-deficit/hyperactivity disorder: Randomized double-blind studydisorder: Randomized double-blind study(2012) (2012) Human PsychopharmacologyHuman Psychopharmacology, 27 (4), pp. 411-, 27 (4), pp. 411-418. Cited 4 times.418. Cited 4 times.

15- Mohammadi, M.R., Soleimani, A.A., 15- Mohammadi, M.R., Soleimani, A.A., Farahmand, Z., Keshavarzi, S., Ahmadi, N.Farahmand, Z., Keshavarzi, S., Ahmadi, N.A comparison of effectiveness of regulation A comparison of effectiveness of regulation of of working memory functionworking memory function and and methylphenidate on remediation of attention methylphenidate on remediation of attention deficit hyperactivity disorder (ADHD)deficit hyperactivity disorder (ADHD)(2014) (2014) Iranian Journal of Iranian Journal of PsychiatryPsychiatry, 9 (1), pp. 25-30. , 9 (1), pp. 25-30. 

3434

Conclusions from trialConclusions from trial Medication is more powerfulMedication is more powerful than than

cognitive behavioural therapy (CBT)cognitive behavioural therapy (CBT)

Research treatmentResearch treatment better than routine better than routine

Many advantages in Many advantages in adding medication adding medication

to behavioural to behavioural

3535

Comparison of treatments (1)Comparison of treatments (1)Meta analysis of 124 trialsMeta analysis of 124 trials

Comparison of treatments (1)Comparison of treatments (1)Meta analysis of 124 trialsMeta analysis of 124 trials

0

0/2

0/4

0/6

0/8

1

1/2

1/4

SD

Stimulant Tricyclic Behaviour

Effect size:hyperactivity

Effect size: CPT

Pre-post differences in means / SD pre-treatment

3636

PET studies show that drugs binds predominantly PET studies show that drugs binds predominantly to to striatumstriatum in the human brain where it binds to DA in the human brain where it binds to DA transporters.transporters.

Where does drugs bind in the human brain?

3737

Pharmacokinetics ofPharmacokinetics of MethylphenidateMethylphenidate in Human Brainin Human Brain

Methylphenidate when injected intravenously enters Methylphenidate when injected intravenously enters the brain rapidly but has a slow clearancethe brain rapidly but has a slow clearance

3838

نوروترانسميترها

ADHD نوروترانس0ميترهاي متع0ددي در فيزيوپ0اتولوژي

Locusنقش دارند از مطالعات حيواني مشخص شده كه

ceruleus داراي نرونه00اي نورآدنرژي00ك ف00راوان ميباش00د و

دارد. اين فرض0يه ADHDنقش كلي0دي در فيزيوپ0اتولوژي

دارن0د يع0ني ADHDب0ا داروه0ايي ك0ه نقش مثبت در درم0ان

محركها تأييد ميگردد.

در حقيقت محركه0ا از طري0ق ت0أثير ب0ر روي ن0ور اپي نف0رين

دوپامين و مي عمل و ريتالين مانند محركها نمايند.

ه00ا دكس00تروآمفتامين از طري00ق اف00زايش كاتك00ل آمين

(اف00زايش آزادس00ازي و جلوگ00يري از بازج00ذب آنه00ا) ت00أثير

.درماني دارند.

3939

Ritalin Binding to Dopamine TransportersRitalin Binding to Dopamine Transporters

Oral MP at therapeutic doses occupies > 50 % DA Oral MP at therapeutic doses occupies > 50 % DA transporters. Estimated EDtransporters. Estimated ED5050 (dose required to occupy (dose required to occupy 50% of the DA transporters) corresponds to 0.25 mg/kg.50% of the DA transporters) corresponds to 0.25 mg/kg.

0

20

40

60

80

100

0.0 0.2 0.4 0.6 0.8 1.0

DA

T O

ccu

pan

cy (

%)

Dose (mg/kg)

typical dose(0.5 mg/kg)

4040

What are the effects of therapeutic doses of oral MP on extracellular DA?

DA

DA

DA

DA DA DA

DA

Without MP

Hypothesis 1Autoreceptor activation decreases DA release blunting DA signals.

Hypothesis 2DAT blockade amplifies DA signals.

DA

DA

DA

DADA

DA

MP

With MP

DA

DA

DADA DADA

DA

DA

DA

DA

DA

DA

DADA

DADA

DADA

MP

4141

Placebo 20 mg 40 mg

What are the levels of DA transporter blockade achieved by MP at the doses used therapeutically for the treatment of ADHD?

MP given orally at therapeutic doses bindsvery efficiently to DA transporters.

4242

DA

DA

DADA DADA

DA

DADA

DA

DADA

DADA

DADA

DA

DADA DA

DA

Amplification of DA signals would Amplification of DA signals would enhance task-specific signaling (DA enhance task-specific signaling (DA decreases background firing and decreases background firing and increases signal-to-noise in target increases signal-to-noise in target neurons), improving attention and neurons), improving attention and decreasing distractibility decreasing distractibility

MP

ADHD Without MP ADHD With MP

MP’s increase of extracellular DA would amplify the weak DA signals in ADHD subjects.

4343

Neuromodulator آدنوزين يك

مهاري نورومدوالتور نقش آدن0وزين بعن0وان ي0ك

مه0اري در سيس0تم اعص0اب مرك0زي در دو

بي0ان ش0ده اس0ت. مطالع0ات ده0ه گذش0ته

متع00ددي ب00ر روي حيوان00ات ب00ازگو كنن00ده

ب0ر روي بس0ياري از مه0اري آدن0وزيننقش

نوروترانس0ميترها از جمل0ه ن0وراپي نف0رين و

آنتاگونيس0تهاي آدن0وزين اس0ت . ل0ذا دوپ0امين

ميتوانند در درمانمانند كافئين و تئوفيلين

ADHD باشند مؤثر.

4444

انواع آدنوزينآدن0وزين بعن0وان ي0ك نروم0دوالتور در دس0تگاه عص0بي

  در هم0ه س0يناپس ها وج0ود دارد و از مرك0زي تقريب0اطري0ق گيرن0ده ه0اي اختصاص0ي در س0طح س0لول اث0ر

ميكند. گيرنده هاي آدنوزين به زير گروههايA1 ، A2a ، A2b ، A3,A4

تقس0يم ميش0وند. اين گيرن0ده ه0ا توزي0ع گس0ترده اي دارن00د و ب00ا بس00ياري از سيس00تم ه00اي CNSدر

نوروترنس000ميتري در تعام000ل هس000تند. ب000ر همين مبناس00ت ك00ه تص00ور ميش00ود از تركيب00ات م00ؤثر ب00ر گيرن0ده ه0اي آدن0وزين ميت0وان در درم0ان بس0ياري از

. اختالالت عصبي رواني استفاده كرد

4545

DA

DA

DA

DA DADA

DA

DA

DA

DA

DA

DA

DA

DA

DADA

DADA

AdenosineAdenosine

�Adenosine: Inhibitory Neuromodulator

4646

اگر مكانيسم اثر داروهاي محرك مانند Ritalin آزاد سازي

دوپامين و نور اپي نفرين باشد آنگاه مهاركننده هاي

گزانتيني آدنوزين مانندكافئين و بخصوص تئوفيلين ميتوانند

كاربرد درماني داشته باشند زيرا آدنوزين اثر مهاري بر

لذا ؛ روي آزاد سازي دوپامين و نوراپي نفرين دارد

مهاركننده هاي آدنوزين مانند تئوفيلين باعث افزايش

بعبارتي با اما .فعاليت دوپامين و نور اپي نفرين مي شوند

Ritalin لذا در اين مطالعه ؛بصورت غير مستقيم

مكانيسم مشابه

ما براي اولين بار Ritalin . را با تئوفيلين مقايسه مي كنيم

اثر بخشي

مكانيسم اثر تئوفيلين

4747

DA

DA

DA

DA DADA

DA

DA

DA

DA

DA

DA

DA

DA

DADA

DADA

Theophyline

�Theophyline Mechanism

4848

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