Table 2.

Overview of the activity of heroin and its metabolites at opioid receptors.

			Heroin	6-MAM	Morphine	M6G	references
	MOP	affinity	<6MAM «M	>H < M	»H > 6MAM ≥ M6G	≤M	[12, 83, 84, 86, 109–112, 119, 120, 126]
		efficacy	=6MAM > M M6G	=H > M M6G	<H 6MAM ≤ M6G	<H 6MAM ≥ M
		potency	«6MAM M M6G	»H = M M6G	»H = 6MAM ≤ M6G	»H = 6MAM ≥ M
	DOP	affinity	<6MAM < M	>H > M	>H < 6MAM < M6G	≥M	[91, 92, 119, 120, 126–128]
		efficacy			=M6G	=M
		potency			=M6G	=M
	KOP	affinity	<6MAM M	>H = M	»M6G	«M	[109, 119, 127, 128]
		efficacy			=M6G	=M
		potency			>M6G	<M
Splice variants	MOP-1r	affinity			≥M6G	≤M	[112, 120, 121]
	MOP-2r	affinity			>M6G	<M
	MOP gene exon1 KO		Analgesic activity retained	Analgesic activity retained	Analgesic activity not retained	Analgesic activity retained	[87] but see also [89, 90]
	MOP gene exon2 KO			Analgesic activity not retained	Analgesic activity retained	Analgesic activity not retained	[88] but see also [89]
	MOP gene exon11 KO		Analgesic activity not retained		Analgesic activity retained	Analgesic activity not retained	[166]

Affinity for the receptor was expressed either by the inhibitory constant Ki, that describes the binding affinity for a ligand that displaces a tracer saturation at the receptor, or by the half-maximal inhibitory concentration IC50, that is the concentration of a ligand that reduces the binding of a tracer to its receptor (or the biological activity of interest) by 50%. Efficacy was expressed by E_max, that is the maximal response achievable from an agent/drug. Potency was expressed either by IC50 (see above) or EC50, intended as the concentration of a drug at which 50% of its maximum effect is achieved. To compare heroin and its metabolites, « and » indicate a value ten-fold less than or greater than; < and > a value less than 10-fold; ≤ and ≥ indicate that studies are not consistent and/or different test assays were used. Data from studies using antisense probes are not reported.

H heroin, M morphine, 6MAM 6-monoacetylmorphine, M6G morphine-6-glucuronide, MOP mu opioid peptide receptor, DOP delta opioid peptide receptor, KOP kappa opioid peptide receptor, KO knock-out mice.