4-NEMD

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4-NEMD

Systematic (IUPAC) name
4-(1-naphthalen- 1-ylethyl)- 1H-imidazole
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	137967-81-8
ATC code	?
PubChem	CID 132110
ChemSpider	24531958^Y
Chemical data
Formula	C₁₅H₁₄N₂
Mol. mass	222.285 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C15H14N2/c1-11(15-9-16-10-17-15)13-8-4-6-12-5-2-3-7-14(12)13/h2-11H,1H3,(H,16,17)/t11-/m0/s1^Y Key:DZSQSLQSMKNVBV-NSHDSACASA-N^Y
Y(what is this?) (verify)

4-NEMD is a potent sedative drug which acts as a selective alpha-2 adrenergic agonist. It is closely related to dexmedetomidine but is several times more potent.^[1] Like other alpha-2 agonists, it produces sedative and muscle relaxant effects but without producing respiratory depression. It is not currently used in medicine but has been researched as the basis for a potential new generation of alpha-2 agonist drugs,^[2]^[3] which may have selectivity for the different subtypes of the alpha-2 receptor.^[4] It has two isomers, with the (S) isomer being the more potent, as with medetomidine.^[5] 4-NEMD was also investigated by the United States military as an anaesthetic agent, most likely for use in surgery but possibly also for use as a non-lethal incapacitating agent.^[6]

[edit] References

^ Hong, SS; Romstedt, KJ; Feller, DR; Hsu, FL; Cupps, TL; Lyon, RA; Miller, DD (1994). "A structure-activity relationship study of benzylic modifications of 4-1-(1-naphthyl)ethyl-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors". Journal of medicinal chemistry 37 (15): 2328–33. doi:10.1021/jm00041a011. PMID 7914537.
^ Zhang, X; Yao, XT; Dalton, JT; Shams, G; Lei, L; Patil, PN; Feller, DR; Hsu, FL et al. (1996). "Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine". Journal of medicinal chemistry 39 (15): 3001–13. doi:10.1021/jm9506074. PMID 8709134.
^ Zhang, X; De Los Angeles, JE; He, MY; Dalton, JT; Shams, G; Lei, L; Patil, PN; Feller, DR et al. (1997). "Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket"". Journal of medicinal chemistry 40 (19): 3014–24. doi:10.1021/jm960642q. PMID 9301663.
^ Lalchandani, SG; Zhang, X; Hong, SS; Liggett, SB; Li, W; Moore Bm, 2nd; Miller, DD; Feller, DR (2004). "Medetomidine analogs as selective agonists for the human alpha2-adrenoceptors". Biochemical pharmacology 67 (1): 87–96. doi:10.1016/j.bcp.2003.08.043. PMID 14667931.
^ Hong, SS; Romstedt, KJ; Feller, DR; Hsu, FL; George, C; Cupps, TL; Lyon, RA; Miller, DD (1992). "Resolution and adrenergic activities of the optical isomers of 4-1-(1-naphthyl)ethyl-1H-imidazole". Chirality 4 (7): 432–8. doi:10.1002/chir.530040706. PMID 1361151.
^ Fu-Lian Hsu and William P. Ashman. 4-(1-(1-naphthalenyl)ethyl)- 1H- imidazole, method of making and use as an anesthetic agent. US patent 5151526.

Adrenergics

Receptor ligands

α₁	Agonists: 5-FNE • 6-FNE • Amidephrine • Anisodamine • Anisodine • Cirazoline • Dipivefrine • Dopamine • Ephedrine • Epinephrine (Adrenaline) • Etilefrine • Ethylnorepinephrine • Indanidine • Levonordefrin • Metaraminol • Methoxamine • Methyldopa • Midodrine • Naphazoline • Norepinephrine (Noradrenaline) • Octopamine • Oxymetazoline • Phenylephrine • Phenylpropanolamine • Pseudoephedrine • Synephrine • Tetrahydrozoline Antagonists: Abanoquil • Adimolol • Ajmalicine • Alfuzosin • Amosulalol • Arotinolol • Atiprosin • Benoxathian • Buflomedil • Bunazosin • Carvedilol • CI-926 • Corynanthine • Dapiprazole • DL-017 • Domesticine • Doxazosin • Eugenodilol • Fenspiride • GYKI-12,743 • GYKI-16,084 • Indoramin • Ketanserin • L-765,314 • Labetalol • Mephendioxan • Metazosin • Monatepil • Moxisylyte (Thymoxamine) • Naftopidil • Nantenine • Neldazosin • Nicergoline • Niguldipine • Pelanserin • Phendioxan • Phenoxybenzamine • Phentolamine • Piperoxan • Prazosin • Quinazosin • Ritanserin • RS-97,078 • SGB-1,534 • Silodosin • SL-89.0591 • Spiperone • Talipexole • Tamsulosin • Terazosin • Tibalosin • Tiodazosin • Tipentosin • Tolazoline • Trimazosin • Upidosin • Urapidil • Zolertine * Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole all antagonize α₁-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.

α₂	Agonists: (R)-3-Nitrobiphenyline • 4-NEMD • 6-FNE • Amitraz • Apraclonidine • Brimonidine • Cannabivarin • Clonidine • Detomidine • Dexmedetomidine • Dihydroergotamine • Dipivefrine • Dopamine • Ephedrine • Ergotamine • Epinephrine (Adrenaline) • Esproquin • Etilefrine • Ethylnorepinephrine • Guanabenz • Guanfacine • Guanoxabenz • Levonordefrin • Lofexidine • Medetomidine • Methyldopa • Mivazerol • Naphazoline • Norepinephrine (Noradrenaline) • Phenylpropanolamine • Piperoxan • Pseudoephedrine • Rilmenidine • Romifidine • Talipexole • Tetrahydrozoline • Tizanidine • Tolonidine • Urapidil • Xylazine • Xylometazoline Antagonists: 1-PP • Adimolol • Aptazapine • Atipamezole • BRL-44408 • Buflomedil • Cirazoline • Efaroxan • Esmirtazapine • Fenmetozole • Fluparoxan • GYKI-12,743 • GYKI-16,084 • Idazoxan • Mianserin • Mirtazapine • MK-912 • NAN-190 • Olanzapine • Phentolamine • Phenoxybenzamine • Piperoxan • Piribedil • Rauwolscine • Rotigotine • SB-269,970 • Setiptiline • Spiroxatrine • Sunepitron • Tolazoline • Yohimbine * Note that many atypical antipsychotics and azapirones like buspirone and gepirone (via metabolite 1-PP) antagonize α₂-adrenergic receptors as well.

β	Agonists: 2-FNE • 5-FNE • Amibegron • Arbutamine • Arformoterol • Arotinolol • BAAM • Bambuterol • Befunolol • Bitolterol • Broxaterol • Buphenine • Carbuterol • Cimaterol • Clenbuterol • Denopamine • Deterenol • Dipivefrine • Dobutamine • Dopamine • Dopexamine • Ephedrine • Epinephrine (Adrenaline) • Etafedrine • Etilefrine • Ethylnorepinephrine • Fenoterol • Formoterol • Hexoprenaline • Higenamine • Indacaterol • Isoetarine • Isoprenaline (Isoproterenol) • Isoxsuprine • Labetalol • Levonordefrin • Levosalbutamol • Mabuterol • Methoxyphenamine • Methyldopa • N-Isopropyloctopamine • Norepinephrine (Noradrenaline) • Orciprenaline • Oxyfedrine • Phenylpropanolamine • Pirbuterol • Prenalterol • Ractopamine • Procaterol • Pseudoephedrine • Reproterol • Rimiterol • Ritodrine • Salbutamol (Albuterol) • Salmeterol • Solabegron • Terbutaline • Tretoquinol • Tulobuterol • Xamoterol • Zilpaterol • Zinterol Antagonists: Acebutolol • Adaprolol • Adimolol • Afurolol • Alprenolol • Alprenoxime • Amosulalol • Ancarolol • Arnolol • Arotinolol • Atenolol • Befunolol • Betaxolol • Bevantolol • Bisoprolol • Bopindolol • Bormetolol • Bornaprolol • Brefonalol • Bucindolol • Bucumolol • Bufetolol • Buftiralol • Bufuralol • Bunitrolol • Bunolol • Bupranolol • Burocrolol • Butaxamine • Butidrine • Butofilolol • Capsinolol • Carazolol • Carpindolol • Carteolol • Carvedilol • Celiprolol • Cetamolol • Cicloprolol • Cinamolol • Cloranolol • Cyanopindolol • Dalbraminol • Dexpropranolol • Diacetolol • Dichloroisoprenaline • Dihydroalprenolol • Dilevalol • Diprafenone • Draquinolol • Dropranolol • Ecastolol • Epanolol • Ericolol • Ersentilide • Esatenolol • Esmolol • Esprolol • Eugenodilol • Exaprolol • Falintolol • Flestolol • Flusoxolol • Hydroxycarteolol • Hydroxytertatolol • ICI-118,551 • Idropranolol • Indenolol • Indopanolol • Iodocyanopindolol • Iprocrolol • Isoxaprolol • Isamoltane • Labetalol • Landiolol • Levobetaxolol • Levobunolol • Levocicloprolol • Levomoprolol • Medroxalol • Mepindolol • Metalol • Metipranolol • Metoprolol • Moprolol • Nadolol • Nadoxolol • Nafetolol • Nebivolol • Neraminol • Nifenalol • Nipradilol • Oberadilol • Oxprenolol • Pacrinolol • Pafenolol • Pamatolol • Pargolol • Parodilol • Penbutolol • Penirolol • PhQA-33 • Pindolol • Pirepolol • Practolol • Primidolol • Procinolol • Pronethalol • Propafenone • Propranolol • Ridazolol • Ronactolol • Soquinolol • Sotalol • Spirendolol • SR 59230A • Sulfinalol • TA-2005 • Talinolol • Tazolol • Teoprolol • Tertatolol • Terthianolol • Tienoxolol • Tilisolol • Timolol • Tiprenolol • Tolamolol • Toliprolol • Tribendilol • Trigevolol • Xibenolol • Xipranolol

Reuptake inhibitors

NET	Selective norepinephrine reuptake inhibitors: Amedalin • Atomoxetine (Tomoxetine) • Ciclazindol • Daledalin • Esreboxetine • Lortalamine • Mazindol • Nisoxetine • Reboxetine • Talopram • Talsupram • Tandamine • Viloxazine; Norepinephrine-dopamine reuptake inhibitors: Amineptine • Bupropion (Amfebutamone) • Fencamine • Fencamfamine • Lefetamine • Levophacetoperane • LR-5182 • Manifaxine • Methylphenidate • Nomifensine • O-2172 • Radafaxine; Serotonin-norepinephrine reuptake inhibitors: Bicifadine • Desvenlafaxine • Duloxetine • Eclanamine • Levomilnacipran • Milnacipran • Sibutramine • Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors: Brasofensine • Diclofensine • DOV-102,677 • DOV-21,947 • DOV-216,303 • JNJ-7925476 • JZ-IV-10 • Methylnaphthidate • Naphyrone • NS-2359 • PRC200-SS • SEP-225,289 • SEP-227,162 • Tesofensine; Tricyclic antidepressants: Amitriptyline • Butriptyline • Cianopramine • Clomipramine • Desipramine • Dosulepin • Doxepin • Imipramine • Lofepramine • melitracen • Nortriptyline • Protriptyline • Trimipramine; Tetracyclic antidepressants: Amoxapine • Maprotiline • Mianserin • Oxaprotiline • Setiptiline; Others: Cocaine • CP-39,332 • EXP-561 • Fezolamine • Ginkgo biloba • Indeloxazine • Nefazodone • Nefopam • Pridefrine • Tapentadol • Teniloxazine • Tramadol • Ziprasidone

VMAT	Ibogaine • Reserpine • Tetrabenazine

Releasing agents

Morpholines: Fenbutrazate • Morazone • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-OH-PEA • 4-CAB • 4-FA • 4-FMA • 4-MA • 4-MMA • Alfetamine • Amfecloral • Amfepentorex • Amfepramone • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Me-PEA • BDB • Benzphetamine • BOH • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • D-Deprenyl • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, metamfepramone) • DMA • DMMA • EBDB • Ephedrine • Ethcathinone • Ethylamphetamine • Ethylone • Famprofazone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • IAP • IMP • L-Deprenyl (Selegiline) • Lisdexamfetamine • Lophophine • MBDB • MDA (Tenamfetamine) • MDEA • MDMA • MDMPEA • MDOH • MDPEA • Mefenorex • Mephedrone • Mephentermine • Methamphetamine (Dextromethamphetamine, Levomethamphetamine) • Methcathinone • Methedrone • Methylone • NAP • Ortetamine • Paredrine • pBA • pCA • Pentorex (Phenpentermine) • Phenethylamine • Pholedrine • Phenpromethamine • Phentermine • Phenylpropanolamine • pIA • Prenylamine • Propylamphetamine • Pseudoephedrine • Tiflorex • Tyramine • Xylopropamine • Zylofuramine; Piperazines: 2C-B-BZP • BZP • MBZP • mCPP • MDBZP • MeOPP • pFPP; Others: 2-Amino-1,2-dihydronaphthalene • 2-Aminoindane • 2-Aminotetralin • 2-Benzylpiperidine • 4-Benzylpiperidine • 5-IAI • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanorex • Isometheptene • Methylhexanamine • Octodrine • Phthalimidopropiophenone • Propylhexedrine (Levopropylhexedrine) • Tuaminoheptane

Enzyme inhibitors

Anabolism

PAH	3,4-Dihydroxystyrene

TH	3-Iodotyrosine • Aquayamycin • Bulbocapnine • Metirosine • Oudenone

AAAD	Benserazide • Carbidopa • Genistein • Methyldopa

DBH	Bupicomide • Disulfiram • Dopastin • Fusaric acid • Nepicastat • Phenopicolinic acid • Tropolone

PNMT	CGS-19281A • SKF-64139 • SKF-7698

Catabolism

MAO	Nonselective: Benmoxin • Caroxazone • Echinopsidine • Furazolidone • Hydralazine • Indantadol • Iproclozide • Iproniazid • Isocarboxazid • Isoniazid • Linezolid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Paraxazone • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Procarbazine • Safrazine • Tranylcypromine; MAO-A selective: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Clorgiline • Esuprone • Harmala alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima; MAO-B selective: D-Deprenyl • Selegiline (L-Deprenyl) • Ladostigil • Lazabemide • Milacemide • Mofegiline • Pargyline • Rasagiline • Safinamide * Note that MAO-B inhibitors also influence norepinephrine/epinephrine levels since they inhibit the breakdown of their precursor dopamine.

COMT	Entacapone • Tolcapone

Others

Precursors	L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa) → Dopamine • L-DOPS (Droxidopa)

Cofactors	Ferrous Iron (Fe²⁺) • S-Adenosyl-L-Methionine • Vitamin B₃ (Niacin, Nicotinamide → NADPH) • Vitamin B₆ (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal Phosphate) • Vitamin B₉ (Folic acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn²⁺)

Others	Activity enhancers: BPAP • PPAP; Release blockers: Bethanidine • Bretylium • Guanadrel • Guanazodine • Guanclofine • Guanethidine • Guanoxan; Toxins: Oxidopamine (6-Hydroxydopamine)

List of adrenergic drugs

v · d · eHypnotics/Sedatives (N05C)

GABA_A Agonists/PAMs	Barbiturates: Allobarbital • Amobarbital • Aprobarbital • Barbital • Butabarbital • Butobarbital • Cyclobarbital • Ethallobarbital • Heptabarbital • Hexobarbital • Mephobarbital • Methohexital • Pentobarbital • Phenobarbital • Proxibarbal • Reposal • Secobarbital • Talbutal • Thiamylal • Thiopental • Vinbarbital • Vinylbital; Benzodiazepines: Brotizolam • Cinolazepam • Climazolam • Doxefazepam • Estazolam • Flunitrazepam • Flurazepam • Flutoprazepam • Haloxazolam • Loprazolam • Lormetazepam • Midazolam • Nimetazepam • Nitrazepam • Quazepam • Temazepam • Triazolam; Carbamates: Carisoprodol • Ethinamate • Hexapropymate • Meprobamate • Methocarbamol • Procymate • Tybamate; Neuroactive Steroids: Acebrochol • Allopregnanolone • Alphadolone • Alphaxolone • Eltanolone • Ganaxolone • Hydroxydione • Minaxolone • Org 20599 • Org 21465 • Tetrahydrodeoxycorticosterone; Nonbenzodiazepines: CL-218,872 • Eszopiclone • Indiplon • JM-1232 • Lirequinil • Necopidem • Pazinaclone • ROD-188 • Saripidem • Suproclone • Suriclone • SX-3228 • U-89843A • U-90042 • Zaleplon • Zolpidem • Zopiclone; Phenols: Fospropofol • Propofol; Piperidinediones: Glutethimide • Methyprylon • Pyrithyldione • Piperidione; Quinazolinones: Afloqualone • Cloroqualone • Diproqualone • Etaqualone • Mebroqualone • Mecloqualone • Methaqualone • Methylmethaqualone • Nitromethaqualone; Others: 2-Methyl-2-butanol • Acetophenone • Acetylglycinamide chloral hydrate • Bromide (Lithium bromide, Potassium bromide, Sodium bromide) • Centalun • Chloral hydrate • Chloralose • Chloralodol • Clomethiazole • Dichloralphenazone • Ethanol (Alcohol) • Ethchlorvynol • Etomidate • Gaboxadol • Loreclezole • Methylpentynol • Metomidate • Paraldehyde • Petrichloral • Sulfonmethane • Trichloroethanol • Triclofos • Valerenic acid (Valerian)

GABA_B Agonists	1,4-Butanediol • Aceburic acid • GABOB • GHB • GBL • GVL

H₁ Inverse agonists	Antihistamines: Captodiame • Cyproheptadine • Dimenhydrinate • Diphenhydramine • Doxylamine • Hydroxyzine • Methapyrilene • Pheniramine • Promethazine • Propiomazine; Others: Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Tetracyclic antidepressants (Mianserin, Mirtazapine, etc.) • Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.)

α₁-Adrenergic Antagonists	Mianserin • Niaprazine • Trazodone; Others: Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.)

α₂-Adrenergic Agonists	4-NEMD • Clonidine • Detomidine • Dexmedetomidine • Lofexidine • Medetomidine • Romifidine • Tizanidine • Xylazine

5-HT_2A Antagonists	Eplivanserin • Niaprazine • Pruvanserin • Trazodone • Volinanserin; Others: Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Tetracyclic antidepressants (Mianserin, Mirtazapine, etc.) • Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.)

Melatonin Agonists	Agomelatine • LY-156,735 • Melatonin • Ramelteon • Tasimelteon

Orexin Antagonists	Almorexant • SB-334,867 • SB-408,124 • SB-649,868 • Suvorexant • TCS-OX2-29

Others	Acecarbromal • Apronal • Bromisoval • Cannabidiol (Cannabis) • Carbromal • Embutramide • Evoxine • Fenadiazole • Gabapentin • Kavalactones (Kava) • Mephenoxalone • Opiates/Opioids (Hydrocodone, Morphine (Opium), etc.) • Passion flower • Scopolamine (Mandrake) • Valnoctamide