Tesamorelin/Ipamorelin Blend 11mg/6mg

Tesamorelin (TH9507) e um(a) sintetico(a) 44-aminoacido analog of endogenous GHRH with a peso molecular of 5135.9 Da. It foi desenvolvido(a) por Theratechnologies Inc. to overcome the inherent instability of native GHRH, que has a meia-vida of apenas 3–8 minutes due to rapido(a) cleavage by DPP-4. [1] [2]

Key Structural Feature: A trans-3-hexenoic acid group is anchored para o(a) N-terminal tyrosine (Tyr1), rendering o peptideo resistant to DPP-4 degradacao and extending the meia-vida to aproximadamente 26–38 minutes. C-terminal is amidated (-NH₂). [3]

Regulatory Status:

• FDA: Approved as Egrifta SV / Egrifta WR for HIV-associated lipodystrophy (excess abdominal fat reduction). NOT indicated for perda de peso. [4]
• EMA: Application withdrawn; not marketed no(a) EU. [6]
• WADA: Prohibited (S2 — Peptide Hormones, Growth Factors). [5]

Developer: Theratechnologies Inc. (Montreal, Canada) — originally designated TH9507.

Pharmacokinetic Highlights:

• Bioavailability: <4% (subcutaneo(a))
• Half-Life: ~26–38 min (SC); ~11 min (1.28 mg WR formulation)
• Route: Subcutaneous injection (abdomen)
• Standard Dose: 2 mg SC daily (Egrifta SV); 1.28 mg SC daily (Egrifta WR, bioequivalent)
• Pulsatility: Preserves natural pulsatile GH secretion (diferentemente de rhGH)

1. Receptor Target — GHRH Receptor

Tesamorelin acts como um(a) specific agonist para o(a) GHRH receptor (GHRHr), a seven-transmembrane G protein-coupled receptor (GPCR) located on somatotroph cells no(a) anterior pituitary gland. Binding potency is comparable to endogenous GHRH. [7]

2. DPP-4 Resistance

The trans-3-hexenoic acid modification no(a) N-terminal Tyr1 acts como um(a) chemical shield against DPP-4 cleavage. Native GHRH is rapidamente degradado(a) (T½ ~5 min); Tesamorelin's modification extends stability to ~26–38 min. [3]

3. Sinalizacao a Jusante Cascade

Gₛ → Adenylyl Cyclase → cAMP → PKA → Ca²⁺ Influx → GH Exocytosis:

1. Receptor ativacao desencadeia the Gₛα subunit
2. Gₛα estimula adenylyl cyclase, converting ATP to cAMP
3. Elevated cAMP ativa Protein Kinase A (PKA)
4. PKA opens voltage-gated Ca²⁺ channels → calcium influx
5. Ca²⁺ desencadeia exocytosis of pre-stored GH vesicles
6. Simultaneamente, cAMP promove GH gene transcricao (new GH synthesis) [7]

The product supplied here is for uso em pesquisa apenas independentemente de regulatory status of related formulations.

4. Selectivity

Tesamorelin is highly selective para o(a) GHRH receptor. It does not significantly alter TSH, LH, ACTH, or Prolactin levels. Diferentemente de GHRPs (e.g., Ipamorelin), it nao bind the ghrelin receptor. [9]

5. Cellular and Tissue-Level Effects

Adipose Tissue:

• Selectively reduz visceral tecido adiposo (VAT) by ~15–18%, minimal effect on subcutaneo(a) fat [10]
• Activates hormone-sensitive lipase (HSL), inibe lipoprotein lipase (LPL)
• Visceral fat cells have higher GH receptor density, explaining selectivity

Hepatic (Liver):

• Reduces hepatico(a) fat (~37% relative reduction) [11]
• Reduces de novo lipogenesis, aprimora fatty acid oxidation
• Prevents progression of liver fibrose (10.5% vs 37.5% progression, P=0.04) [11]

Musculoskeletal:

• Promotes protein synthesis, aumenta trunk lean mass and muscle area [12]
• Improves muscle density (myosteatosis reduction)

Nervous System:

• Improves executive function and verbal memory in MCI/aging [13]
• Increases GABA levels, modula amyloid-beta pathways

6. Comparison with Related Molecules

7. Pharmacokinetics

💊 HIV-Associated Lipodystrophy (FDA-registered)

O(a) principal clinical application. Two pivotal Phase 3 trials (n=816) demonstrated 14–18% VAT reduction with 2 mg SC daily, with improvements in triglycerides (-12.3%), body image, and waist circumference. Reductions were manteve over 52 weeks but reversed upon discontinuation. [4] [10]

🫁 NAFLD / NASH

A 12-month RCT (n=61) in HIV-infected sujeitos de estudo showed 37% hepatico(a) fat reduction, with 35% achieving normal hepatico(a) fat fraction (<5%). Criticamente, Tesamorelin preveniu progression of liver fibrose (10.5% vs 37.5% in placebo, P=0.04). [11]

🧠 Cognitivo Function / MCI

In a blinded RCT (n=152) of healthy older adults and MCI sujeitos de estudo, 1 mg diariamente por 20 weeks melhorou executive function (P=0.005) and global cognition (P=0.03), with IGF-1 increasing +117%. Mechanisms involve aumentou GABA and amyloid-beta modulacao. [13]

🦴 Peripheral Nerve Regeneration

Preclinical GH models showed aprimorou median regeneracao nervosa (axon density P<0.005, myelin thickness P<0.0001) and melhorou muscle re-innervation (38% vs 27.9%, P<0.02). Tesamorelin is identificado(a) como the optimal agent for human traducao. [14]

❤️ Cardiovascular Risk Reduction

Reduces triglycerides and melhora carotid intima-media thickness (cIMT). VAT reduction is theorized to lower atherosclerotic doenca risco cardiovascular. Long-term desfechos cardiovasculares remain under study. [15]

💪 Sarcopenia / Muscle Quality

Increases musculo esqueletico density and area (particularmente trunk region), independente de changes in muscle mass quantity. Replaces hypertrophic lipid-engorged fat cells with healthy tissue. [12]

🍬 Metabolic Syndrome / Type 2 Diabetes

A tolerability study in T2D sujeitos de estudo (n=53) demonstrated neutral glucose effects — no significant changes in fasting glucose, HbA1c, or insulin response vs placebo. No entanto, Phase 3 HIV data showed aumentou HbA1c risk (HR 3.3 vs placebo), warranting monitoring. [16]

Clinical Trials

Reported Tolerability Profile

Established through 800+ sujeitos de estudo in Phase 3 trials. [4]

• Common (>5%): Arthralgia, injection site erythema/pruritus, pain in extremity, periferico(a) edema, myalgia
• Hypersensitivity: 3.6–4% (pruritus, erythema, flushing, urticaria)
• Glucose: Increased risk of HbA1c ≥6.5% (HR 3.3 vs placebo); monitor glucose
• Reproductive: Pregnancy Category X — hydrocephaly in rat offspring at 2–4x human dose; retardou skull ossification at lower doses
• Contraindications: Active malignancy, hypophysectomy/pituitary tumor, pregnancy, hypersensitivity