{"product_id":"nsi-189-60x30mg","title":"NSI-189 100x30mg","description":"\u003cp class=\"\" data-end=\"920\" data-start=\"352\"\u003e\u003cstrong\u003e\u003cstrong data-start=\"377\" data-end=\"392\"\u003e\u003cspan style=\"color: rgb(255, 42, 0);\"\u003e                                         \u003cspan style=\"text-decoration: underline;\"\u003eNOT \u003c\/span\u003e\u003c\/span\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cspan style=\"color: rgb(255, 42, 0); text-decoration: underline;\"\u003eFOR HUMAN CONSUMPTION\u003c\/span\u003e\u003c\/span\u003e\u003c\/strong\u003e\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp class=\"\" data-end=\"920\" data-start=\"352\"\u003e\u003cstrong\u003eNSI-189 \u003cmeta charset=\"UTF-8\"\u003e\u003c\/strong\u003eis an \u003cstrong data-start=\"98\" data-end=\"168\"\u003eorally bioavailable, benzylpiperazine-aminopyridine small molecule\u003c\/strong\u003e originally developed to \u003cstrong data-start=\"193\" data-end=\"231\"\u003estimulate hippocampal neurogenesis\u003c\/strong\u003e and improve \u003cstrong data-start=\"244\" data-end=\"266\"\u003emood and cognition\u003c\/strong\u003e. It is \u003cstrong data-start=\"274\" data-end=\"290\"\u003enot approved\u003c\/strong\u003e by any regulator. After \u003cstrong data-start=\"315\" data-end=\"326\"\u003ePhase 1\u003c\/strong\u003e safety and signal-finding studies in \u003cstrong data-start=\"364\" data-end=\"399\"\u003emajor depressive disorder (MDD)\u003c\/strong\u003e, a \u003cstrong data-start=\"403\" data-end=\"414\"\u003ePhase 2\u003c\/strong\u003e program did \u003cstrong data-start=\"427\" data-end=\"439\"\u003enot meet\u003c\/strong\u003e its primary endpoint; development has largely \u003cstrong data-start=\"486\" data-end=\"497\"\u003estalled\u003c\/strong\u003e. Preclinical data indicate \u003cstrong data-start=\"525\" data-end=\"575\"\u003epro-neurogenic, synaptogenic, and neurotrophic\u003c\/strong\u003e effects in hippocampus with downstream impacts on \u003cstrong data-start=\"626\" data-end=\"646\"\u003estress circuitry\u003c\/strong\u003e and \u003cstrong data-start=\"651\" data-end=\"664\"\u003ecognition\u003c\/strong\u003e.\u003c\/p\u003e\n\u003chr data-start=\"667\" data-end=\"670\"\u003e\n\u003ch3 data-start=\"672\" data-end=\"730\"\u003eAdditional Benefits of NSI-189 Now Under Investigation\u003c\/h3\u003e\n\u003cdiv class=\"_tableContainer_1rjym_1\"\u003e\n\u003cdiv class=\"group _tableWrapper_1rjym_13 flex w-fit flex-col-reverse\" tabindex=\"-1\"\u003e\n\u003ctable data-start=\"732\" data-end=\"2832\" class=\"w-fit min-w-(--thread-content-width)\"\u003e\n\u003cthead data-start=\"732\" data-end=\"760\"\u003e\n\u003ctr data-start=\"732\" data-end=\"760\"\u003e\n\u003cth data-start=\"732\" data-end=\"742\" data-col-size=\"md\"\u003eBenefit\u003c\/th\u003e\n\u003cth data-start=\"742\" data-end=\"760\" data-col-size=\"xl\"\u003eKey take-aways\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody data-start=\"771\" data-end=\"2832\"\u003e\n\u003ctr data-start=\"771\" data-end=\"1028\"\u003e\n\u003ctd data-start=\"771\" data-end=\"804\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"773\" data-end=\"803\"\u003e1 Hippocampal neurogenesis\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"804\" data-end=\"1028\"\u003eIn vitro and rodent studies show \u003cstrong data-start=\"839\" data-end=\"872\"\u003eproliferation\/differentiation\u003c\/strong\u003e of hippocampal precursors and \u003cstrong data-start=\"903\" data-end=\"920\"\u003espine density\u003c\/strong\u003e increases; memory behaviors improve in stress\/lesion models. \u003cem data-start=\"982\" data-end=\"1026\"\u003eStem Cell Reports; Journal of Neuroscience\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"1029\" data-end=\"1306\"\u003e\n\u003ctd data-start=\"1029\" data-end=\"1065\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"1031\" data-end=\"1064\"\u003e2 Antidepressant signal (MDD)\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"1065\" data-end=\"1306\"\u003eEarly Phase 1b showed \u003cstrong data-start=\"1089\" data-end=\"1117\"\u003eexploratory improvements\u003c\/strong\u003e on depression scales; the \u003cstrong data-start=\"1144\" data-end=\"1155\"\u003ePhase 2\u003c\/strong\u003eRCT failed its primary endpoint but suggested \u003cstrong data-start=\"1202\" data-end=\"1224\"\u003esubset\/time-course\u003c\/strong\u003e signals—insufficient for approval. \u003cem data-start=\"1260\" data-end=\"1304\"\u003eMolecular Psychiatry; Depression \u0026amp; Anxiety\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"1307\" data-end=\"1566\"\u003e\n\u003ctd data-start=\"1307\" data-end=\"1371\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"1309\" data-end=\"1370\"\u003e3 Cognitive enhancement (processing speed\/working memory)\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"1371\" data-end=\"1566\"\u003eRodent data and small human exploratory tasks suggested \u003cstrong data-start=\"1429\" data-end=\"1458\"\u003emodest cognitive benefits\u003c\/strong\u003e, especially in \u003cstrong data-start=\"1474\" data-end=\"1494\"\u003eprocessing speed\u003c\/strong\u003e and \u003cstrong data-start=\"1499\" data-end=\"1518\"\u003everbal learning\u003c\/strong\u003e domains. \u003cem data-start=\"1528\" data-end=\"1564\"\u003eNeuropsychopharmacology; CNS Drugs\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"1567\" data-end=\"1790\"\u003e\n\u003ctd data-start=\"1567\" data-end=\"1598\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"1569\" data-end=\"1597\"\u003e4 Anhedonia \u0026amp; motivation\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"1598\" data-end=\"1790\" data-col-size=\"xl\"\u003ePreclinical stress paradigms show \u003cstrong data-start=\"1634\" data-end=\"1656\"\u003esucrose preference\u003c\/strong\u003e and \u003cstrong data-start=\"1661\" data-end=\"1683\"\u003eeffort-based tasks\u003c\/strong\u003eimprovements consistent with mesolimbic normalization. \u003cem data-start=\"1739\" data-end=\"1788\"\u003eBiological Psychiatry; Translational Psychiatry\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"1791\" data-end=\"2002\"\u003e\n\u003ctd data-start=\"1791\" data-end=\"1834\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"1793\" data-end=\"1833\"\u003e5 Neuroprotection after ischemia\/TBI\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"1834\" data-end=\"2002\"\u003eIn stroke\/TBI models, NSI-189 \u003cstrong data-start=\"1866\" data-end=\"1915\"\u003ereduced lesion-associated behavioral deficits\u003c\/strong\u003e and supported \u003cstrong data-start=\"1930\" data-end=\"1949\"\u003eneurite\/synapse\u003c\/strong\u003e recovery. \u003cem data-start=\"1960\" data-end=\"2000\"\u003eBrain Research; Experimental Neurology\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"2003\" data-end=\"2222\"\u003e\n\u003ctd data-start=\"2003\" data-end=\"2052\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"2005\" data-end=\"2051\"\u003e6 Anti-inflammatory\/neuroimmune modulation\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"2052\" data-end=\"2222\"\u003eDown-shift of \u003cstrong data-start=\"2068\" data-end=\"2088\"\u003emicroglial NF-κB\u003c\/strong\u003e and cytokines (IL-1β, TNF-α) reported alongside neurogenesis; causal links remain exploratory. \u003cem data-start=\"2184\" data-end=\"2220\"\u003eGlia; Journal of Neuroinflammation\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"2223\" data-end=\"2419\"\u003e\n\u003ctd data-start=\"2223\" data-end=\"2257\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"2225\" data-end=\"2256\"\u003e7 Stress-axis normalization\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"2257\" data-end=\"2419\"\u003eRodent work shows \u003cstrong data-start=\"2277\" data-end=\"2289\"\u003eHPA-axis\u003c\/strong\u003e re-tuning with lower corticosterone reactivity and improved \u003cstrong data-start=\"2350\" data-end=\"2374\"\u003ehippocampal feedback\u003c\/strong\u003e. \u003cem data-start=\"2376\" data-end=\"2417\"\u003eEndocrinology; Psychoneuroendocrinology\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"2420\" data-end=\"2599\"\u003e\n\u003ctd data-start=\"2420\" data-end=\"2453\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"2422\" data-end=\"2452\"\u003e8 Neuroplasticity in aging\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"2453\" data-end=\"2599\" data-col-size=\"xl\"\u003eSignals for \u003cstrong data-start=\"2467\" data-end=\"2489\"\u003ehippocampal volume\u003c\/strong\u003e preservation and memory tasks in aged rodents; human aging data absent. \u003cem data-start=\"2562\" data-end=\"2597\"\u003eAging Cell; Neurobiology of Aging\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"2600\" data-end=\"2832\"\u003e\n\u003ctd data-start=\"2600\" data-end=\"2644\" data-col-size=\"md\"\u003e\u003cstrong data-start=\"2602\" data-end=\"2643\"\u003e9 Adjunct in PTSD\/cognitive syndromes\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"xl\" data-start=\"2644\" data-end=\"2832\"\u003eConcept: pair neurogenesis with psychotherapy\/rehab to consolidate learning; only preclinical or hypothesis-driven studies so far. \u003cem data-start=\"2777\" data-end=\"2830\"\u003eFrontiers in Psychiatry; Behavioural Brain Research\u003c\/em\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr data-start=\"2834\" data-end=\"2837\"\u003e\n\u003ch2 data-start=\"2839\" data-end=\"2874\"\u003e2. Molecular Mechanism of Action\u003c\/h2\u003e\n\u003ch3 data-start=\"2876\" data-end=\"2918\"\u003e2.1 Pharmacodynamics (working model)\u003c\/h3\u003e\n\u003cul data-start=\"2919\" data-end=\"3427\"\u003e\n\u003cli data-start=\"2919\" data-end=\"3144\"\u003e\n\u003cp data-start=\"2921\" data-end=\"3144\"\u003e\u003cstrong data-start=\"2921\" data-end=\"2955\"\u003eNeurogenesis \u0026amp; synaptogenesis:\u003c\/strong\u003e Up-regulates \u003cstrong data-start=\"2969\" data-end=\"2977\"\u003eBDNF\u003c\/strong\u003e, \u003cstrong data-start=\"2979\" data-end=\"2987\"\u003eCREB\u003c\/strong\u003e, \u003cstrong data-start=\"2989\" data-end=\"3001\"\u003eMAPK\/ERK\u003c\/strong\u003e, and \u003cstrong data-start=\"3007\" data-end=\"3024\"\u003ePI3K–Akt–mTOR\u003c\/strong\u003e pathways → \u003cstrong data-start=\"3036\" data-end=\"3064\"\u003eprogenitor proliferation\u003c\/strong\u003e, \u003cstrong data-start=\"3066\" data-end=\"3095\"\u003edendritic spine formation\u003c\/strong\u003e, and \u003cstrong data-start=\"3101\" data-end=\"3122\"\u003esynaptic proteins\u003c\/strong\u003e (PSD-95, synapsin).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"3145\" data-end=\"3292\"\u003e\n\u003cp data-start=\"3147\" data-end=\"3292\"\u003e\u003cstrong data-start=\"3147\" data-end=\"3180\"\u003eNeuroimmune \u0026amp; HPA modulation:\u003c\/strong\u003e Restraint of \u003cstrong data-start=\"3194\" data-end=\"3203\"\u003eNF-κB\u003c\/strong\u003e signaling and improved \u003cstrong data-start=\"3227\" data-end=\"3254\"\u003eglucocorticoid feedback\u003c\/strong\u003e in hippocampus → stress resilience.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"3293\" data-end=\"3427\"\u003e\n\u003cp data-start=\"3295\" data-end=\"3427\"\u003e\u003cstrong data-start=\"3295\" data-end=\"3343\"\u003eNot a monoaminergic reuptake inhibitor\/MAOI.\u003c\/strong\u003e Any serotonergic\/dopaminergic effects appear \u003cstrong data-start=\"3389\" data-end=\"3403\"\u003edownstream\u003c\/strong\u003e of plasticity cascades.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3 data-start=\"3429\" data-end=\"3456\"\u003e2.2 Down-stream biology\u003c\/h3\u003e\n\u003cdiv class=\"_tableContainer_1rjym_1\"\u003e\n\u003cdiv class=\"group _tableWrapper_1rjym_13 flex w-fit flex-col-reverse\" tabindex=\"-1\"\u003e\n\u003ctable data-start=\"3458\" data-end=\"3797\" class=\"w-fit min-w-(--thread-content-width)\"\u003e\n\u003cthead data-start=\"3458\" data-end=\"3500\"\u003e\n\u003ctr data-start=\"3458\" data-end=\"3500\"\u003e\n\u003cth data-start=\"3458\" data-end=\"3468\" data-col-size=\"sm\"\u003ePathway\u003c\/th\u003e\n\u003cth data-start=\"3468\" data-end=\"3489\" data-col-size=\"md\"\u003eFunctional outcome\u003c\/th\u003e\n\u003cth data-start=\"3489\" data-end=\"3500\" data-col-size=\"sm\"\u003eContext\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody data-start=\"3515\" data-end=\"3797\"\u003e\n\u003ctr data-start=\"3515\" data-end=\"3601\"\u003e\n\u003ctd data-start=\"3515\" data-end=\"3542\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"3517\" data-end=\"3541\"\u003eBDNF–TrkB → ERK\/CREB\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"3542\" data-end=\"3586\" data-col-size=\"md\"\u003ePlasticity gene induction, mood\/cognition\u003c\/td\u003e\n\u003ctd data-col-size=\"sm\" data-start=\"3586\" data-end=\"3601\"\u003eHippocampus\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"3602\" data-end=\"3672\"\u003e\n\u003ctd data-start=\"3602\" data-end=\"3622\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"3604\" data-end=\"3621\"\u003ePI3K–Akt–mTOR\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"3622\" data-end=\"3656\" data-col-size=\"md\"\u003eCell survival, dendritic growth\u003c\/td\u003e\n\u003ctd data-col-size=\"sm\" data-start=\"3656\" data-end=\"3672\"\u003eHippo\/cortex\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"3673\" data-end=\"3739\"\u003e\n\u003ctd data-start=\"3673\" data-end=\"3695\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"3675\" data-end=\"3694\"\u003eNF-κB restraint\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"3695\" data-end=\"3726\" data-col-size=\"md\"\u003e↓ Pro-inflammatory cytokines\u003c\/td\u003e\n\u003ctd data-col-size=\"sm\" data-start=\"3726\" data-end=\"3739\"\u003eMicroglia\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"3740\" data-end=\"3797\"\u003e\n\u003ctd data-start=\"3740\" data-end=\"3760\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"3742\" data-end=\"3759\"\u003eHPA re-tuning\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-col-size=\"md\" data-start=\"3760\" data-end=\"3782\"\u003eStress reactivity ↓\u003c\/td\u003e\n\u003ctd data-col-size=\"sm\" data-start=\"3782\" data-end=\"3797\"\u003eLimbic loop\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr data-start=\"3799\" data-end=\"3802\"\u003e\n\u003ch2 data-start=\"3804\" data-end=\"3826\"\u003e3. Pharmacokinetics\u003c\/h2\u003e\n\u003cul data-start=\"3828\" data-end=\"4260\"\u003e\n\u003cli data-start=\"3828\" data-end=\"3869\"\u003e\n\u003cp data-start=\"3830\" data-end=\"3869\"\u003e\u003cstrong data-start=\"3830\" data-end=\"3840\"\u003eRoute:\u003c\/strong\u003e \u003cstrong data-start=\"3841\" data-end=\"3849\"\u003eOral\u003c\/strong\u003e (phosphate salt).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"3870\" data-end=\"3953\"\u003e\n\u003cp data-start=\"3872\" data-end=\"3953\"\u003e\u003cstrong data-start=\"3872\" data-end=\"3894\"\u003eBrain penetration:\u003c\/strong\u003e Demonstrated in animals; human CNS levels not published.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"3954\" data-end=\"4074\"\u003e\n\u003cp data-start=\"3956\" data-end=\"4074\"\u003e\u003cstrong data-start=\"3956\" data-end=\"3983\"\u003eHalf-life\/steady state:\u003c\/strong\u003e \u003cstrong data-start=\"3984\" data-end=\"4016\"\u003eHours to low-teens half-life\u003c\/strong\u003e reported; once- or twice-daily regimens used in trials.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"4075\" data-end=\"4170\"\u003e\n\u003cp data-start=\"4077\" data-end=\"4170\"\u003e\u003cstrong data-start=\"4077\" data-end=\"4092\"\u003eMetabolism:\u003c\/strong\u003e Hepatic oxidative pathways (exact CYP liabilities not fully characterized).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"4171\" data-end=\"4260\"\u003e\n\u003cp data-start=\"4173\" data-end=\"4260\"\u003e\u003cstrong data-start=\"4173\" data-end=\"4202\"\u003eFood effect\/interactions:\u003c\/strong\u003e Limited public data; not a classic CYP inducer\/inhibitor.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003chr data-start=\"4262\" data-end=\"4265\"\u003e\n\u003ch2 data-start=\"4267\" data-end=\"4303\"\u003e4. Clinical Evidence (high-level)\u003c\/h2\u003e\n\u003cul data-start=\"4305\" data-end=\"4735\"\u003e\n\u003cli data-start=\"4305\" data-end=\"4435\"\u003e\n\u003cp data-start=\"4307\" data-end=\"4435\"\u003e\u003cstrong data-start=\"4307\" data-end=\"4327\"\u003ePhase 1b in MDD:\u003c\/strong\u003e Generally \u003cstrong data-start=\"4338\" data-end=\"4356\"\u003ewell tolerated\u003c\/strong\u003e; exploratory antidepressant and cognitive \u003cstrong data-start=\"4399\" data-end=\"4410\"\u003esignals\u003c\/strong\u003e across several scales.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"4436\" data-end=\"4619\"\u003e\n\u003cp data-start=\"4438\" data-end=\"4619\"\u003e\u003cstrong data-start=\"4438\" data-end=\"4457\"\u003ePhase 2 in MDD:\u003c\/strong\u003e \u003cstrong data-start=\"4458\" data-end=\"4491\"\u003eDid not meet primary endpoint\u003c\/strong\u003e vs placebo; some \u003cstrong data-start=\"4509\" data-end=\"4534\"\u003esecondary\/exploratory\u003c\/strong\u003e outcomes hinted at benefit in subgroups\/time windows—insufficient for advancement.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"4620\" data-end=\"4735\"\u003e\n\u003cp data-start=\"4622\" data-end=\"4735\"\u003e\u003cstrong data-start=\"4622\" data-end=\"4645\"\u003eImaging\/biomarkers:\u003c\/strong\u003e Small datasets explored \u003cstrong data-start=\"4670\" data-end=\"4697\"\u003ehippocampal volumetrics\u003c\/strong\u003e and peripheral \u003cstrong data-start=\"4713\" data-end=\"4721\"\u003eBDNF\u003c\/strong\u003e—inconclusive.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cblockquote data-start=\"4737\" data-end=\"4952\"\u003e\n\u003cp data-start=\"4739\" data-end=\"4952\"\u003e\u003cstrong data-start=\"4739\" data-end=\"4765\"\u003eEvidence quality note:\u003c\/strong\u003e Strong \u003cstrong data-start=\"4773\" data-end=\"4801\"\u003epreclinical plausibility\u003c\/strong\u003e with \u003cstrong data-start=\"4807\" data-end=\"4831\"\u003eneurogenesis\/circuit\u003c\/strong\u003e biology; \u003cstrong data-start=\"4841\" data-end=\"4868\"\u003ehuman efficacy unproven\u003c\/strong\u003e after a negative Phase 2. Any clinical use should be confined to research settings.\u003c\/p\u003e\n\u003c\/blockquote\u003e\n\u003chr data-start=\"4954\" data-end=\"4957\"\u003e\n\u003ch2 data-start=\"4959\" data-end=\"5005\"\u003e5. Emerging Clinical Interests (conceptual)\u003c\/h2\u003e\n\u003cdiv class=\"_tableContainer_1rjym_1\"\u003e\n\u003cdiv class=\"group _tableWrapper_1rjym_13 flex w-fit flex-col-reverse\" tabindex=\"-1\"\u003e\n\u003ctable data-start=\"5007\" data-end=\"5377\" class=\"w-fit min-w-(--thread-content-width)\"\u003e\n\u003cthead data-start=\"5007\" data-end=\"5037\"\u003e\n\u003ctr data-start=\"5007\" data-end=\"5037\"\u003e\n\u003cth data-start=\"5007\" data-end=\"5015\" data-col-size=\"sm\"\u003eField\u003c\/th\u003e\n\u003cth data-start=\"5015\" data-end=\"5027\" data-col-size=\"sm\"\u003eRationale\u003c\/th\u003e\n\u003cth data-start=\"5027\" data-end=\"5037\" data-col-size=\"sm\"\u003eStatus\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody data-start=\"5052\" data-end=\"5377\"\u003e\n\u003ctr data-start=\"5052\" data-end=\"5131\"\u003e\n\u003ctd data-start=\"5052\" data-end=\"5089\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"5054\" data-end=\"5088\"\u003eTreatment-resistant depression\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"5089\" data-end=\"5120\" data-col-size=\"sm\"\u003ePlasticity beyond monoamines\u003c\/td\u003e\n\u003ctd data-start=\"5120\" data-end=\"5131\" data-col-size=\"sm\"\u003eConcept\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"5132\" data-end=\"5237\"\u003e\n\u003ctd data-start=\"5132\" data-end=\"5170\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"5134\" data-end=\"5169\"\u003ePost-stroke\/TBI cognitive rehab\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"5170\" data-end=\"5208\" data-col-size=\"sm\"\u003ePairing synaptogenesis with therapy\u003c\/td\u003e\n\u003ctd data-start=\"5208\" data-end=\"5237\" data-col-size=\"sm\"\u003ePreclinical\/early concept\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"5238\" data-end=\"5290\"\u003e\n\u003ctd data-start=\"5238\" data-end=\"5249\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"5240\" data-end=\"5248\"\u003ePTSD\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"5249\" data-end=\"5279\" data-col-size=\"sm\"\u003eExtinction learning support\u003c\/td\u003e\n\u003ctd data-start=\"5279\" data-end=\"5290\" data-col-size=\"sm\"\u003eConcept\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"5291\" data-end=\"5377\"\u003e\n\u003ctd data-start=\"5291\" data-end=\"5327\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"5293\" data-end=\"5326\"\u003eAge-related cognitive decline\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"5327\" data-end=\"5354\" data-col-size=\"sm\"\u003eHippocampal neurogenesis\u003c\/td\u003e\n\u003ctd data-start=\"5354\" data-end=\"5377\" data-col-size=\"sm\"\u003ePreclinical concept\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr data-start=\"5379\" data-end=\"5382\"\u003e\n\u003ch2 data-start=\"5384\" data-end=\"5413\"\u003e6. Safety and Tolerability\u003c\/h2\u003e\n\u003cul data-start=\"5415\" data-end=\"6166\"\u003e\n\u003cli data-start=\"5415\" data-end=\"5554\"\u003e\n\u003cp data-start=\"5417\" data-end=\"5554\"\u003e\u003cstrong data-start=\"5417\" data-end=\"5442\"\u003eCommon AEs in trials:\u003c\/strong\u003e \u003cstrong data-start=\"5443\" data-end=\"5455\"\u003eHeadache\u003c\/strong\u003e, \u003cstrong data-start=\"5457\" data-end=\"5470\"\u003edizziness\u003c\/strong\u003e, \u003cstrong data-start=\"5472\" data-end=\"5495\"\u003esomnolence\/insomnia\u003c\/strong\u003e, \u003cstrong data-start=\"5497\" data-end=\"5507\"\u003enausea\u003c\/strong\u003e, \u003cstrong data-start=\"5509\" data-end=\"5520\"\u003efatigue\u003c\/strong\u003e—generally \u003cstrong data-start=\"5531\" data-end=\"5551\"\u003emild to moderate\u003c\/strong\u003e.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"5555\" data-end=\"5630\"\u003e\n\u003cp data-start=\"5557\" data-end=\"5630\"\u003e\u003cstrong data-start=\"5557\" data-end=\"5577\"\u003eVitals\/labs\/ECG:\u003c\/strong\u003e No consistent safety signal in short-term studies.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"5631\" data-end=\"5743\"\u003e\n\u003cp data-start=\"5633\" data-end=\"5743\"\u003e\u003cstrong data-start=\"5633\" data-end=\"5654\"\u003eNeuropsychiatric:\u003c\/strong\u003e Activation\/insomnia in a subset; monitor for \u003cstrong data-start=\"5700\" data-end=\"5724\"\u003eanxiety or agitation\u003c\/strong\u003e early in dosing.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"5744\" data-end=\"5875\"\u003e\n\u003cp data-start=\"5746\" data-end=\"5875\"\u003e\u003cstrong data-start=\"5746\" data-end=\"5773\"\u003eSuicidality monitoring:\u003c\/strong\u003e Standard for antidepressant investigations—no clear excess signal reported, but vigilance required.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"5876\" data-end=\"5941\"\u003e\n\u003cp data-start=\"5878\" data-end=\"5941\"\u003e\u003cstrong data-start=\"5878\" data-end=\"5899\"\u003eLong-term safety:\u003c\/strong\u003e Unknown (no lengthy exposure datasets).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"5942\" data-end=\"6166\"\u003e\n\u003cp data-start=\"5944\" data-end=\"6166\"\u003e\u003cstrong data-start=\"5944\" data-end=\"5966\"\u003eDrug interactions:\u003c\/strong\u003e Limited data; because the MOA is \u003cstrong data-start=\"6000\" data-end=\"6021\"\u003enon-monoaminergic\u003c\/strong\u003e, risk of \u003cstrong data-start=\"6031\" data-end=\"6053\"\u003eserotonin syndrome\u003c\/strong\u003e appears low when combined with SSRIs\/SNRIs, but combination evidence is sparse—use caution in research settings.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp data-start=\"6168\" data-end=\"6235\"\u003e\u003cstrong data-start=\"6168\" data-end=\"6235\"\u003eComparative snapshot (neuroplasticity-oriented antidepressants)\u003c\/strong\u003e\u003c\/p\u003e\n\u003cdiv class=\"_tableContainer_1rjym_1\"\u003e\n\u003cdiv class=\"group _tableWrapper_1rjym_13 flex w-fit flex-col-reverse\" tabindex=\"-1\"\u003e\n\u003ctable data-start=\"6237\" data-end=\"6654\" class=\"w-fit min-w-(--thread-content-width)\"\u003e\n\u003cthead data-start=\"6237\" data-end=\"6306\"\u003e\n\u003ctr data-start=\"6237\" data-end=\"6306\"\u003e\n\u003cth data-start=\"6237\" data-end=\"6247\" data-col-size=\"sm\"\u003eFeature\u003c\/th\u003e\n\u003cth data-start=\"6247\" data-end=\"6261\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6249\" data-end=\"6260\"\u003eNSI-189\u003c\/strong\u003e\u003c\/th\u003e\n\u003cth data-start=\"6261\" data-end=\"6287\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6263\" data-end=\"6286\"\u003eKetamine\/Esketamine\u003c\/strong\u003e\u003c\/th\u003e\n\u003cth data-start=\"6287\" data-end=\"6306\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6289\" data-end=\"6304\"\u003eSSRIs\/SNRIs\u003c\/strong\u003e\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody data-start=\"6325\" data-end=\"6654\"\u003e\n\u003ctr data-start=\"6325\" data-end=\"6438\"\u003e\n\u003ctd data-start=\"6325\" data-end=\"6342\" data-col-size=\"sm\"\u003ePrimary action\u003c\/td\u003e\n\u003ctd data-start=\"6342\" data-end=\"6382\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6344\" data-end=\"6381\"\u003eNeurogenesis\/BDNF–CREB (putative)\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"6382\" data-end=\"6415\" data-col-size=\"sm\"\u003eRapid glutamatergic plasticity\u003c\/td\u003e\n\u003ctd data-start=\"6415\" data-end=\"6438\" data-col-size=\"sm\"\u003eMonoamine transport\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"6439\" data-end=\"6499\"\u003e\n\u003ctd data-start=\"6439\" data-end=\"6447\" data-col-size=\"sm\"\u003eOnset\u003c\/td\u003e\n\u003ctd data-start=\"6447\" data-end=\"6465\" data-col-size=\"sm\"\u003eGradual (weeks)\u003c\/td\u003e\n\u003ctd data-start=\"6465\" data-end=\"6490\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6467\" data-end=\"6489\"\u003eRapid (hours–days)\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"6490\" data-end=\"6499\" data-col-size=\"sm\"\u003eWeeks\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"6500\" data-end=\"6587\"\u003e\n\u003ctd data-start=\"6500\" data-end=\"6511\" data-col-size=\"sm\"\u003eEvidence\u003c\/td\u003e\n\u003ctd data-start=\"6511\" data-end=\"6542\" data-col-size=\"sm\"\u003e\u003cstrong data-start=\"6513\" data-end=\"6541\"\u003eNegative Phase 2 primary\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd data-start=\"6542\" data-end=\"6564\" data-col-size=\"sm\"\u003eRobust TRD efficacy\u003c\/td\u003e\n\u003ctd data-start=\"6564\" data-end=\"6587\" data-col-size=\"sm\"\u003eRobust MDD efficacy\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-start=\"6588\" data-end=\"6654\"\u003e\n\u003ctd data-start=\"6588\" data-end=\"6606\" data-col-size=\"sm\"\u003eAbuse liability\u003c\/td\u003e\n\u003ctd data-start=\"6606\" data-end=\"6623\" data-col-size=\"sm\"\u003eLow (expected)\u003c\/td\u003e\n\u003ctd data-start=\"6623\" data-end=\"6647\" data-col-size=\"sm\"\u003eModerate (controlled)\u003c\/td\u003e\n\u003ctd data-start=\"6647\" data-end=\"6654\" data-col-size=\"sm\"\u003eLow\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr data-start=\"6656\" data-end=\"6659\"\u003e\n\u003ch2 data-start=\"6661\" data-end=\"6687\"\u003e7. Regulatory Landscape\u003c\/h2\u003e\n\u003cul data-start=\"6689\" data-end=\"6916\"\u003e\n\u003cli data-start=\"6689\" data-end=\"6759\"\u003e\n\u003cp data-start=\"6691\" data-end=\"6759\"\u003e\u003cstrong data-start=\"6691\" data-end=\"6707\"\u003eNot approved\u003c\/strong\u003e (no active late-stage programs publicly ongoing).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"6760\" data-end=\"6916\"\u003e\n\u003cp data-start=\"6762\" data-end=\"6916\"\u003eAny availability is via \u003cstrong data-start=\"6786\" data-end=\"6807\"\u003eresearch channels\u003c\/strong\u003e; consumer “nootropic” products are \u003cstrong data-start=\"6843\" data-end=\"6858\"\u003eunregulated\u003c\/strong\u003e and may be \u003cstrong data-start=\"6870\" data-end=\"6887\"\u003emisidentified\u003c\/strong\u003e—avoid outside formal trials.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003chr data-start=\"6918\" data-end=\"6921\"\u003e\n\u003ch2 data-start=\"6923\" data-end=\"6963\"\u003e8. Practical Take \u0026amp; Future Directions\u003c\/h2\u003e\n\u003cul data-start=\"6965\" data-end=\"7635\"\u003e\n\u003cli data-start=\"6965\" data-end=\"7062\"\u003e\n\u003cp data-start=\"6967\" data-end=\"7062\"\u003e\u003cstrong data-start=\"6967\" data-end=\"6986\"\u003eCurrent stance:\u003c\/strong\u003e NSI-189 remains \u003cstrong data-start=\"7003\" data-end=\"7019\"\u003eexperimental\u003c\/strong\u003e with \u003cstrong data-start=\"7025\" data-end=\"7059\"\u003einsufficient clinical efficacy\u003c\/strong\u003e.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"7063\" data-end=\"7333\"\u003e\n\u003cp data-start=\"7065\" data-end=\"7333\"\u003e\u003cstrong data-start=\"7065\" data-end=\"7095\"\u003eIf pursued scientifically:\u003c\/strong\u003e Target \u003cstrong data-start=\"7103\" data-end=\"7123\"\u003ebiotype-enriched\u003c\/strong\u003e populations (low hippocampal volume, high inflammation, high anhedonia), use \u003cstrong data-start=\"7201\" data-end=\"7227\"\u003eadaptive trial designs\u003c\/strong\u003e, and anchor outcomes with \u003cstrong data-start=\"7254\" data-end=\"7277\"\u003eobjective cognition\u003c\/strong\u003e, \u003cstrong data-start=\"7279\" data-end=\"7302\"\u003edigital phenotyping\u003c\/strong\u003e, and \u003cstrong data-start=\"7308\" data-end=\"7319\"\u003eMRI\/EEG\u003c\/strong\u003e biomarkers.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"7334\" data-end=\"7489\"\u003e\n\u003cp data-start=\"7336\" data-end=\"7489\"\u003e\u003cstrong data-start=\"7336\" data-end=\"7363\"\u003eCombination hypotheses:\u003c\/strong\u003e Pair with \u003cstrong data-start=\"7374\" data-end=\"7397\"\u003epsychotherapy\/rehab\u003c\/strong\u003e, \u003cstrong data-start=\"7399\" data-end=\"7411\"\u003eexercise\u003c\/strong\u003e, or \u003cstrong data-start=\"7416\" data-end=\"7452\"\u003esleep-based plasticity protocols\u003c\/strong\u003e to exploit a pro-neurogenic state.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"7490\" data-end=\"7635\"\u003e\n\u003cp data-start=\"7492\" data-end=\"7635\"\u003e\u003cstrong data-start=\"7492\" data-end=\"7516\"\u003eTranslational needs:\u003c\/strong\u003e Clear \u003cstrong data-start=\"7523\" data-end=\"7555\"\u003etarget engagement biomarkers\u003c\/strong\u003e, refined \u003cstrong data-start=\"7565\" data-end=\"7574\"\u003ePK\/PD\u003c\/strong\u003e, and \u003cstrong data-start=\"7580\" data-end=\"7605\"\u003elonger blinded trials\u003c\/strong\u003e in precisely defined cohorts.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003chr data-start=\"7637\" data-end=\"7640\"\u003e\n\u003ch3 data-start=\"7642\" data-end=\"7665\"\u003eSelected References\u003c\/h3\u003e\n\u003cul data-start=\"7667\" data-end=\"8312\"\u003e\n\u003cli data-start=\"7667\" data-end=\"7782\"\u003e\n\u003cp data-start=\"7669\" data-end=\"7782\"\u003e\u003cem data-start=\"7669\" data-end=\"7713\"\u003eStem Cell Reports; Journal of Neuroscience\u003c\/em\u003e — NSI-189-driven neurogenesis and synaptogenesis in vitro\/in vivo.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"7783\" data-end=\"7923\"\u003e\n\u003cp data-start=\"7785\" data-end=\"7923\"\u003e\u003cem data-start=\"7785\" data-end=\"7840\"\u003eMolecular Psychiatry; Depression \u0026amp; Anxiety; CNS Drugs\u003c\/em\u003e — Phase 1\/2 clinical results in MDD (safety, exploratory signals, Phase 2 miss).\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"7924\" data-end=\"8039\"\u003e\n\u003cp data-start=\"7926\" data-end=\"8039\"\u003e\u003cem data-start=\"7926\" data-end=\"7977\"\u003eNeuropsychopharmacology; Translational Psychiatry\u003c\/em\u003e — Plasticity markers, cognition, and stress-model outcomes.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"8040\" data-end=\"8132\"\u003e\n\u003cp data-start=\"8042\" data-end=\"8132\"\u003e\u003cem data-start=\"8042\" data-end=\"8078\"\u003eGlia; Journal of Neuroinflammation\u003c\/em\u003e — Neuroimmune modulation accompanying neurogenesis.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"8133\" data-end=\"8231\"\u003e\n\u003cp data-start=\"8135\" data-end=\"8231\"\u003e\u003cem data-start=\"8135\" data-end=\"8176\"\u003eEndocrinology; Psychoneuroendocrinology\u003c\/em\u003e — HPA-axis changes linked to hippocampal plasticity.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-start=\"8232\" data-end=\"8312\"\u003e\n\u003cp data-start=\"8234\" data-end=\"8312\"\u003e\u003cem data-start=\"8234\" data-end=\"8274\"\u003eBrain Research; Experimental Neurology\u003c\/em\u003e — Post-stroke\/TBI recovery paradigms.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e","brand":"Mijn winkel","offers":[{"title":"Default Title","offer_id":52684862161234,"sku":null,"price":90.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1048\/0956\/2450\/files\/NSI-189_30mg.png?v=1770834917","url":"https:\/\/sciencepeptideslab.com\/products\/nsi-189-60x30mg","provider":"Science Peptides Lab","version":"1.0","type":"link"}