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Clinical efficacy; No comparator

aOnly selected compounds are shown for purposes of comparing mechanisms/drug classes using data from two major classes of punishment procedures. Only data from systemic dosing are included. Only data from acute dosing are included. Anxiolytic-like effects of some compounds in these assays have been reported in the literature but with other procedures suggested to detect anxioltyic mechanisms (e.g., endocannabinoid uptake or enzyme inhibition;mGlu8 agonists; gabapentin). It must also be noted that sometimes the findings summarized have not been replicated. bA comprehensive review of drug effects under the Vogel conflict procedure and associated mechanisms can be found in Millan (2003). General summaries of data in the Geller-Seifter procedures can be found in McMillan and Leander (1976), Kelleher and Morse (1968). cData included in this table represent results of findings from a host of sources readily accessible in the archival literature;a listing is available upon request from the authors. Data from experiments using rats are used when possible to keep the compound comparisons as uncomplicated as possible. Data are classified by activity on the basis of comparison to the maximal effect observed under the procedure. Maximal effect in each experiment was estimated on the basis of effects of a positive allosteric modulator of GABAA receptors, generally, a benzodiazepine anxiolytic. ++: maximal increase in punished responding at some dose (in comparison with a benzodiazepine anxiolytic if available);+: significant increase but less than maximal;—: no increase in punished responding or decrease at some dose;++? An increase in punished responding was observed but the comparative magnitude of effect relative to a standard was not tested in the same study.

dData from two major types of procedures are compared if available. G-S: Geller-Seifter conflict tests of which there are variants;V: Vogel conflict tests of which there are variants.

eClinical efficacy is in reference to anxiety disorders. Literature inconsistent refers to both the potential qualitative differences observed with the specific compound and/or with discrpencies across compounds within a given mechanism of action.

ACPC 1-aminocyclopropanecarboxylic acid;BW 723C86 1-[5-(2-thienylmethoxy)-1H-3-indoyl] propan-2-amine hydrochloride;£G/S-10608 (±) 1-(3-methyl-4-amino-phenyl)-4-methyl-7,8-methylenedioxy-4,5-dihydro-3-acetyl-2,3-benzodiazepine;EMQMCM ((3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate);8-OH-DPAT 8-hydroxy-2-(di-n-propyl-amino) tetralin;GR205171 (S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino)-2(S)-phenylpiperidine;LY341495 (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid; LY35474 (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate;LY388284 3S,4aR, 6S,8aR-6-((4-carboxyphenyl)methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;MCL0042 1-[2-(4-fluorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]-4- [4-(1-naphthyl) butyl]piperazine;MDL 100,907 R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol; MPEP (2-methyl-6-(phenylethynyl)pyridine);NS11394 [3_-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile]; PD 135,158 N-methyl-D-glucamine; R278995/CRA0450 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-1,2,3,6-tetrahydropyridine-4-carboxamide benzenesulfonate; S32006 N-pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide;S32504 (+)-trans-3,4,4a,5,6,10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth[1,2-b]-1,4-oxazine;SB-399885 N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide;SCH 221510 8-[bis(2-methyl-phenyl)-methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol;SNAP 37889 (1-phenyl-3-[[3-(trifluoromethyl)pheny-l]imino]-1H-indol-2-one;55R149415 (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl] -4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide;TPA023: 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine; WAY 100635 N-[2[4(2-methoxyphenyl)-1-piperazinyl]xethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride.

Punishment Procedures. Table 1. (continued)

Compounda

Mechanism(s)/Classb

Activityc

Procedured

Commente

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Anxiety and Panic Attacks

Anxiety and Panic Attacks

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