Side-by-side · Research reference

5-Amino-1MQvsMK-677

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

AAnimal-StrongDraft8/38 cited

BPhase 2Reviewed13/45 cited

5-Amino-1MQ

NNMT inhibitor · Methylation / SAM modulation

100–200 mgDaily dose (oral)Neelakantan 2018

AnimalEvidence levelNeelakantan 2018

HoursHalf-life (est)

Oral · Once daily fasted

MK-677

Oral GHS · Ibutamoren

10–25 mgDaily dose (oral)Nass 2008

Phase 2Evidence levelMurphy 1998 Nass 2008

~24 hrHalf-lifeNass 2008

Oral capsule · 1×/day

01Mechanism of Action

Parameter

5-Amino-1MQ

MK-677

Primary target

Nicotinamide N-methyltransferase (NNMT)Neelakantan 2018

Ghrelin receptor (GHS-R1a)Murphy 1998

Pathway

NNMT inhibition → preserved cellular SAM + NAD⁺ → restored methylation balance + ↑ thermogenic gene expressionNeelakantan 2018

GHS-R1a → Gαq → Ca²⁺ → sustained GH pulses across 24 hrNass 2008

Downstream effect

Reversal of HFD-induced obesity in murine models; improved metabolic profileNeelakantan 2018

Sustained GH + IGF-1 elevation; appetite stimulation; lean mass preservationNass 2008

Feedback intact?

—

Pulsatile pattern preserved despite long half-lifeMurphy 1998

Origin

Selective small-molecule inhibitor designed in academic medicinal chemistry programsNeelakantan 2018

Non-peptide spiroindane-piperidine small molecule designed at MerckMurphy 1998

Antibody development

—

02Dosage Protocols

Parameter

5-Amino-1MQ

MK-677

Standard dose

100–200 mg / day oralNeelakantan 2018

Anecdotal community range; murine doses scaled.

10–25 mg / day oralNass 2008

25 mg used in Nass 2008 elderly trial; 10–15 mg common community dose.

Frequency

Once daily, fasted

Once daily, oral

Lower / starter dose

50 mg / day

5 mg / day

Evidence basis

Animal-strong; no human RCT dataNeelakantan 2018

Phase 2 trials (Nass 2008, Murphy 1998)Nass 2008 Murphy 1998

Duration

8–12 weeks per cycle

8–16 weeks per cycle (off-cycle to reset receptor sensitivity)

Form

Oral capsule

—

Timing

Morning fasted preferred

Pre-sleep preferred for natural GH pulse alignment

Half-life

Hours (estimated; no human PK published)

~24 hrNass 2008

Once-daily dosing covers 24 hours.

Reconstitution

—

Oral, no reconstitution

04Side Effects & Safety

Parameter

5-Amino-1MQ

MK-677

GI symptoms

Mild nausea (anecdotal)

—

Methylation disruption

Theoretical risk if NNMT is over-inhibited (B vitamin metabolism)

—

Long-term safety

Unknown — no human trials

—

Cancer risk

Unclear — NNMT also studied in oncology contexts

Contraindicated in active malignancy (GH/IGF-1 axis)

Pregnancy / OB

Avoid

Drug interactions

Theoretical with niacin / B-vitamin supplements

—

Increased appetite

—

Strong appetite increase via ghrelin agonism

Water retention

—

Mild edema, paresthesias

Glucose tolerance

—

↑ HbA1c +0.3–0.5% in 2-yr elderly trialNass 2008

IGF-1 elevation

—

+50–100% sustainedNass 2008

Cardiovascular

—

No clear adverse signal in trials; congestive heart failure caution

Drowsiness

—

Common, especially during initial weeks

Absolute Contraindications

5-Amino-1MQ

·Pregnancy / breastfeeding
·Active malignancy

MK-677

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis
·Congestive heart failure (caution)

Relative Contraindications

5-Amino-1MQ

·Methylation-sensitive conditions (MTHFR mutation)
·Concurrent niacin / NAD+ precursor supplementation (theoretical interference)

MK-677

·Untreated diabetes
·Pre-diabetes
·Severe insulin resistance

05Administration Protocol

Parameter

5-Amino-1MQ

MK-677

1. Form

Oral capsule. No injection.

Capsule or oral solution. No injection.

2. Administration

Take with water, fasted preferred.

Oral. Take with or without food.

3. Timing

Morning fasted.

Pre-sleep preferred — aligns with natural GH pulse.

4. Storage

Room temp ≤25 °C, dry place.

Capsule: room temp ≤25 °C, dry place.

5. Caveat

Monitor B-vitamin status with chronic use.

Monitor HbA1c every 8–12 weeks during chronic use.