Side-by-side · Research reference

Kisspeptin-10vsTesofensine

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED10/41 cited

BPhase 3AUTO-DRAFTED10/40 cited

Kisspeptin-10

Neuropeptide · GPR54 Agonist

GnRH pulse generatorPrimary roleSilva 2026

Phase 1/2Clinical stage

GPR54/Kiss1RTarget receptorRønnekleiv 2026

IV / SQ · Investigational

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

Kisspeptin-10

Tesofensine

Primary target

GPR54/Kiss1R on hypothalamic GnRH neuronsRønnekleiv 2026 Collado-Sole 2026

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

Kisspeptin → GPR54 activation → GnRH neuronal depolarization → Pulsatile GnRH release → Pituitary LH/FSH secretionLages 2026 Rønnekleiv 2026

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

Pulsatile LH surge, FSH elevation, gonadal steroidogenesis, gametogenesis initiationLages 2026

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

Yes — integrates estradiol, leptin, and IGF-1 signals to modulate HPG axisSilva 2026 Rønnekleiv 2026

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Origin

C-terminal decapeptide of KISS1 gene product; retains full biological activity of longer kisspeptin isoforms

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

—

02Dosage Protocols

Parameter

Kisspeptin-10

Tesofensine

Clinical trial dose

Phase 1/2 investigational

Dosing protocols vary by indication (hypothalamic amenorrhea, IVF trigger).

—

Route

IV or SQ administration

IV preferred in controlled trials for precise pulsatile delivery.

—

Evidence basis

Phase 1/2 trials

Phase 2b + ongoing Phase 3Astrup 2008

Half-life

Short (minutes)

Rapid clearance; pulsatile dosing mimics physiological GnRH pulse frequency.

~9 days (very long)

Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Frequency

—

Once daily, morning

Lower / starter dose

—

0.125 mg / day

Duration

—

24 weeks per studied cycle

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

04Side Effects & Safety

Parameter

Kisspeptin-10

Tesofensine

Ovarian hyperstimulation

Theoretical risk with supraphysiological dosing in fertility protocols

—

Headache

Mild, reported in early-phase trials

—

Nausea

Transient GI symptoms with IV bolus

Common

Hot flashes

Vasomotor symptoms from LH surge

—

Injection site reaction

Erythema, mild discomfort (SQ route)

—

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Pregnancy / OB

—

Contraindicated

Absolute Contraindications

Kisspeptin-10

·Active pregnancy
·Hormone-sensitive malignancy (breast, ovarian, endometrial)

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

Kisspeptin-10

·Polycystic ovary syndrome (PCOS) without monitoring
·Uncontrolled thyroid dysfunction

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

Kisspeptin-10

Tesofensine

1. Reconstitution (if lyophilized)

Reconstitute with sterile water or saline per protocol. Gently swirl — do not shake. Solution should be clear and colorless.

Oral capsule (investigational; not commercial).

2. Route selection

IV infusion for pulsatile delivery in clinical trials; SQ for outpatient protocols. IV allows precise temporal control of GnRH pulse frequency.

Swallow whole with water, morning only.

3. Timing

Pulsatile dosing (e.g., every 60–90 min) mimics physiological GnRH pulse generator. Single-bolus protocols used for LH surge induction in fertility research.

Morning to mitigate insomnia. Do not dose evening.

4. Monitoring

Serial LH, FSH, estradiol measurements to confirm HPG axis activation. Ultrasound monitoring for ovarian response in fertility applications.

Room temp ≤25 °C, dry place.

5. Storage

Lyophilized: store at 2–8 °C, light-protected. Reconstituted: refrigerate, use within 24–48 hours per protocol.

Monitor BP + HR + mood. Avoid stimulants + MAOIs.