PDE Inhibition and cognition enhancement

Figures & data

Table 1. mRNA expression of different PDE subtypes in selected regions of the human brain relevant for learning and memory (frontal cortex, parietal cortex, temporal cortex, hippocampus, and caudate nucleus).

PDE family	PDE subtype	Strong mRNA expression in selected brain regions relevant for learning and memory	Strong mRNA expression in peripheral tissues
1	A	*	Small intestine
	B	Frontal cortex, parietal cortex, temporal cortex, striatum, hippocampus
	C	Frontal cortex, parietal cortex, hippocampus	pancreas, stomach, small intestine, heart, kidney, bladder, and lung
2	A	Frontal cortex, parietal cortex, striatum, hippocampus	Adrenal gland, liver, pancreas, stomach, small intestine, kidney, bladder, and spleen
3	A	*
	B	*
4	A	Frontal cortex, parietal cortex, temporal cortex	Pancreas, stomach, small intestine, and skeletal muscle
	B	Frontal cortex, parietal cortex, hippocampus	Liver, pancreas, small intestine, skeletal muscle, kidney, bladder, lung, and spleen
	C	*
	D	*
5	A	*
7	A	*
	B	*
8	A	*	Adrenal gland, liver, pancreas, stomach, small intestine, and kidney
	B	Frontal cortex, parietal cortex, temporal cortex, hippocampus	Thyroid, pancreas, small intestine, and kidney
9	A	*	Pancreas, small intestine, kidney, bladder, lung, spleen, and stomach
10	A	Caudate nucleus	Kidney
11	A	*

Only the PDE subtypes with mRNA expression levels of more than 20% compared to the PDE subtype with highest mRNA expression in that region are depicted (based on [17]).

*Expression below 20% of maximally expressed PDE in a brain region.

Table 2. Overview of approved patents of PDE inhibitors claiming a positive effect on learning and memory.

PDE	Application number	Compound class	Company
2	US20010911277 20010723	Alkyl and cycloakyl derivatives	–
2	WO2001EP08609 20010719	–	Bayer
2A	WO2004US10060 20040401	–	Memory Pharmaceuticals Corp.
2A	US20050545501 20050812	–	Memory Pharmaceuticals Corp.
4	US20050536250 20050520		–
4	BG20010105321D 20010309	Substituted 1,8-naphthridin-4(1H)-ones
4	US20040517416 20041208	8-(biaryl) quinolines	Merck
4	US20040484172 20040120	Triazine derivatives	Merck
4	WO2003CA01799 20031119	[various]	Merck
4	US20030622117 20030718	Aminoindazole and aminobenzofuran analogs	Memory Pharmaceuticals Corp.
4	NZ20030547469 20030718	6-amino-1H-indazole and 4-aminobenzofuran compounds	Memory Pharmaceuticals Corp.
4	NZ20030537725 20030718	Aminobenzofuran compounds	Memory Pharmaceuticals Corp.
4	WO2003CA00957 20030623	8-(biaryl) quinolines	Merck
4	WO2002EP07113 20020627	Tyrosine hydrazides	Merck
4	WO2002JP06158 20020620	Pyrrolidine derivatives	Takeda
4	NZ20020527081 20020122	Aniline derivatives	Memory Pharmaceuticals Corp.
4	RU20030124303 20020122	Aniline derivatives	Memori Farmas Jutiklz Corp.
4	US20020054273 20020122	Pyrrole compounds	Icos Corp.
4	YUP57603 20020122	N-substituted aniline and diphenylamine analogs	Memory Pharmaceuticals Corp.
4	US20020051309 20020122	N-substituted aniline and diphenylamine analogs	Memory Pharmaceuticals Corp.
4	US20020030477 20020109	Benzoyl derivatives	Merck
4	NZ19980337698 19980310	Nicotinamide derivatives	Pfizer
4	MX2002PA00293 20020109	–	Memory Pharmaceuticals Corp.
4	EA20020000702 20001220	Substituted 8-arylquinoline compounds	Merck
4	JP19930172024 19930621	1,8-naphthyridine derivative	Green Cross Corp.
4	US20000719467 20001213	Arylalkanoylpyridazine derivatives	MERCK
4	NZ19990504933 19991102	Substituted quinoline-carboxylic acid (pyridinyl)amide compounds	Darwin Discovery Ltd
4	CZ19960000251 19960126	Arylalkylthiadiazinone derivative compounds	Merck
4	WO2006CA01729 20061023	4-oxo-1-3-substituted phenyl-1,4-dihydro-1,8-naphthyridine-3-carboxamide compounds	Merck
4	MX2005PA05413 20050520	4-oxo-1-3-substituted phenyl-1,4-dihydro-1,8-naphthyridine-3-carboxamide compounds	Merck
4	US20050534582 20050511	4-oxo-1-3-substituted phenyl-1,4-dihydro-1,8-naphthyridine-3-carboxamide compounds	Merck
4D(6)	US20030682722 20031010	–	–
4D7	US20040492835 20041202	–	Memory Pharmaceuticals Corp.
7	US20020129270 20020503	Isoxazole derivative compounds	Merck
7	CZ20020001251 20001010	Benzo(thio)pyranoimidazolone derivatives	Merck
9a	EP20100184576 20030811	6-(cyclohexylmethyl)-1-(1-ethylpropyl)-1,5-dihydro-4H-pyrazolo-(3,4-d) -pyrimidin-4-one	Boehringer Ingelheim Int [DE]
9a(?)	US20050524956 20051215	Novel alkyl-substituted pyrazolopyrimidine compounds	Bayer
10	KR20077015027 20070629	Pyrrolidyl derivatives of benzo-fused aza heteroaromatic compounds	Pfizer
10	WO2007IB02382 20070816	Heteroaromatic compounds	Pfizer
10	WO2007IB01696 20070615	Tricyclic heteroaryl compounds	Pfizer
10	US20070298782 20070426	Tricyclic heteraaryi compounds	Pfizer
10	US20070279869 20070209	Quinazoline compounds	Pfizer
10	US20070161718 20070122	Aminophthalazine compounds	Pfizer
10	US20070619218 20070103	Bicyclic heteroaryl compounds	Pfizer
10	WO2006IB03875 20061227	Bicyclic heteroaryl compounds	Pfizer
10	US20050257179 20051024	Pyrrolidyl derivatives of benzo-fused aza heteroaromatic compounds	Pfizer
10	NZ20020518478 20020419	1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline	Pfizer
10A7	US20050546332 20050817	–	Memory Pharmaceuticals Corp.
10A7	WO2004US09878 20040330	–	Memory Pharmaceuticals Corp.
Not specified	KR20090087426 20090916	?	Korea Inst Sci & Tech.
Not specified	US20030694183 20031028	[various]
Not specified	US20020216886 20020813	Nitrosated and/or nitrosylated derivatives	Nitromed, Inc.
Not specified	WO2001JP01720 20010306	Polypeptide

Source: http://www.epo.org/.

Lakics V, Karran EH, Boess FG. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology 2010;59:367-74

 PubMed Web of Science ®Google Scholar