Table 5.

Summary of the involvement of Oprm1 variants in mu opioid analgesia

MOR -1 Variants required for analgesia	Drug	Non-mu opioid receptor	Reference
7TM	Morphine		(8, 20)
	Methadone		(8, 20)
	DAMGO		Figs. 2,3,4
7TM + 6TM	Buprenorphine		(54)
	Endomorphin 1		Fig. 2
	Endomorphin 2		Fig. 2
	DAPP		Figs. 2,3,4
	IDAPP		Figs. 2,3,4
	DPDPE	Delta opioid	(21)
	SNC80	Delta opioid	(21)
6TM	IBNtxA	Unknown	(8, 40, 46)
	Ketocyclazocine	Kappa opioid	(21)
	U50,488H	Kappa opioid	(21)
	Salvinorin A	Kappa opioid	(21)
	Clonidine	α2-adrenergic	(21)
	Dexmedetomidine	α2-adrenergic	(21)

Summary of the requirements of a series of analgesics for various classes of Oprm1 variants based upon analgesia in either knockout models and/or antisense models. Mu analgesics can be subclassified based on their requirements for MOR-1 splice variants. The first category includes drugs that require 7TM variants independent of 6TM variants. The second category requires both 6TM and 7TM variants to be expressed for activity. For the third class of drugs, 6TMs are both necessary and sufficient for activity (e.g. IBNtxA). No non-opioid receptor that is involved with IBNtxA analgesia has yet been identified, but this remains a possibility. A number of non-opioid analgesics that depend upon Oprm1 6TM variants for activity also require their respective non-mu opioid receptor, as indicated in the third column. Delta compounds are unique in that they require both 6TM and 7TM Oprm1 variants as well as delta opioid receptors. It is not clear whether the 6TM variants play a direct role in the targets for these non-mu analgesics (e.g. heterodimerization) or modulate the response through downstream mechanisms