Disease relevance of SKF 81297

• Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out [1].
• In contrast, the therapeutic benefits of D(1) agonists SKF 81297 and dihydrexidine were relatively limited in mild parkinsonism (n = 4) [2].
• The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose-dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia [3].
• SKF 81297, 0.3 mg/kg, induced acute oral dyskinesia and grooming, which were each inhibited by the DA D1 receptor antagonist NNC 756 in a dose-dependent manner [4].

Psychiatry related information on SKF 81297

• In general, SKF-81297 produced a biphasic effect on motor activity (locomotor and rearing activity), which consisted of an initial short inhibition followed by a long-lasting stimulation [5].
• However, while SKF-81297 dose-dependently increased response latency, SCH-23390 did not [6].
• The D1 agonists SKF 38393 and SKF 81297 (3.0 mg/kg, i.p.) significantly reduced the latency period to find a hidden platform in the Morris Water Maze, reflecting improved cognitive functions, while the D1 antagonist SCH 23390 (0.05 mg/kg, i.p.) had no overall significant effect [7].
• In this study, the behavioural response to dopamine D1-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D2-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested [8].
• On the other hand, apomorphine, the D2 agonist quinpirole, or combination of quinpirole and the D1 agonist SKF 81297 induced more stereotyped behavior such as biting or head movements in D2L-/- mice (which express only D2S) than in wild type mice [9].

High impact information on SKF 81297

• A D1 agonist, SKF 81297, inhibited (37.6 +/- 4.7%) NHE activity in brush border membranes of normotensive F2s (systolic blood pressure < 140 mm Hg, n = 7) but not in hypertensive F2s (n = 21) [10].
• Whole-cell patch clamp recordings of acutely dissociated hippocampal pyramidal cells revealed that the D1 dopamine receptor agonist SKF 81297 reduces peak Na(+) current amplitude by 20.5%, as reported previously [11].
• SKF 81297, a D1-like agonist, mimicked DA-induced effect on evoked IPSCs (IC50, 10.9 microM), whereas R(-)-TNPA or (-)-quinpirole, D2-like agonists (30 microM), had little or no effect on the amplitude of evoked IPSCs [12].
• Contrary to this, chronic intermittent stimulation of the motor cortex down-regulated cocaine-induced gene expression in the striatum, but enhanced striatal gene expression induced by a full D1 receptor agonist (SKF 81297) and did not change the early-gene response elicited by a D2 receptor antagonist (haloperidol) [13].
• D1-D2 receptor heterooligomers were internalized when the receptors were coactivated by dopamine or either receptor was singly activated by the D1-selective agonist (+/-)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) or the D2-selective agonist quinpirole [14].

Chemical compound and disease context of SKF 81297

• Effects of intra-accumbal injections of SKF 83959 on locomotor activity were compared to effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonist SCH 39166 [15].
• Furthermore, SKF-81297 decreased cocaine reinstatement and increased response latency only at the highest dose [6].
• The effects of the high-efficacy D1 receptor agonist SKF 81297 and the D2/3 receptor agonist 7-OH-DPAT on brain stimulation reward thresholds and on response latencies in responding for the stimulation, were compared to the effects of subtype-selective receptor antagonists and a dopamine uptake blocker [16].

Biological context of SKF 81297

• The D(1) receptor agonist SKF 81297 increased Ser845 phosphorylation in a concentration- dependent manner, with marked increases occurring within 5 min [17].
• D1 agonists including SKF 81297, SKF 82958, and R(+)-6-Br-APB produced dose-dependent increases in the frequencies of stationary postures and head movements and had little or no effect on either huddling or scratching [18].
• The D1 agonist (+/-)-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) also produced increases in blood pressure and heart rate but was much less potent than either cocaine or SKF 82958 [19].
• We investigated sex differences in the motor responses to the full and selective dopamine D1-like receptor agonist, (+/-)-6-chloro-7,8-dihydroxyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297; 0.3, 3, and 10 mg/kg, s.c.), in non-habituated adult rats [20].

Anatomical context of SKF 81297

• Surface GluR1 labeling on processes of medium spiny neurons and interneurons was increased by brief (5-15 min) incubation with a D1 agonist (1 microm SKF 81297) [21].
• Here, we investigated the effects of a full and selective D1 receptor agonist, SKF-81297, on motor activity and expression of the plasticity-associated gene, c-fos, in the prefrontal cortex and striatum of juvenile and adolescent male rats [5].
• Furthermore, the inhibitory effects on striatal nerve cell firing rate by the D1 receptor agonist SKF 81297 were not different in noninnervated or reinnervated areas of the striatum compared to the control side as seen from the dose-response curves [22].
• Dihydrexidine, SKF 81297 and A-77636 were free of rate effects on midbrain dopamine neurons (up to 10.2 mg/kg) and also did not antagonize the inhibitory effects of quinpirole [23].
• Microinfusion of the D2/3 dopamine receptor antagonist sulpiride ((S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxybenzamide) (1.0 mug) into the nucleus accumbens shell 10 minutes prior to SKF-81297 (1.0 mug) blocked the ability of this D1-like dopamine receptor agonist to reinstate cocaine seeking [24].

Associations of SKF 81297 with other chemical compounds

• After 3 weeks of withdrawal from cocaine self-administration, high intake rats were subsensitive to the ability of the D1 agonist SKF 81297 to inhibit cocaine-seeking behavior elicited by cocaine priming, but supersensitive to cocaine seeking triggered by the D2 agonist quinpirole, when compared to low intake rats [25].
• Furthermore, A53T-tg mice were supersensitive to the D1 receptor agonist SKF 81297 but not to the serotonin1B receptor agonist RU 24969 [26].
• The D1 full agonist, SKF 81297 which produced hyperactivity by itself and the D1 partial agonist, SKF 38393, did not specifically affect ethanol-induced activities [27].
• When striatal slices were incubated with a combination of CGS 21680 and SKF 81297, the effects of the two agonists on both DARPP-32 phosphorylation and cyclic AMP formation were additive [28].
• Perfusion of the higher dose (100 microM) of SKF 81297 enhanced GABA efflux, whereas perfusion of the lower dose (10 microM) decreased GABA efflux [29].

Gene context of SKF 81297

• A maximally effective concentration of SpcAMPS (10 microm) occluded the effect of SKF 81297 (1 microm) on GluR1 externalization [30].
• We show that, in striatal slices, the D2 receptor agonist, quinpirole, strongly inhibits the phosphorylation of DARPP-32 induced by either the D1 receptor agonist, SKF 81297, or the A2A receptor agonist, CGS 21680 [31].
• The full D1 agonist SKF 81297, when administered systemically to control animals, stimulated a dose-dependent increase in locomotor activity [32].
• RESULTS: Reversal of sensitization was produced by repeated administration of either a D1-class agonist (SKF 81297) or the combination of an NMDA receptor antagonist and a D2-class agonist [33].
• When studied in combination with a range of cocaine doses, treatment with the agonists SKF 83959, SKF 77434, SKF 81297, and the antagonist SCH 39166 produced overall rightward and downward shifts in the dose-response function for cocaine self-administration [34].

Analytical, diagnostic and therapeutic context of SKF 81297

• Most interestingly, while prefrontal cortical perfusion of SKF 81297 (100 and 250 microM) had no significant effect on ACh release in post-pubertal sham-operated animals, it significantly stimulated ACh release to approximately 250% baseline at both doses in post-pubertal NVH-lesioned animals [35].
• Moreover, by western blot analysis using an antibody specific for the phosphorylated PKA site Ser845 of GluR1, we observed a marked increase in phosphorylated GluR1 following a 10-min exposure of striatal neurons to 1 microM SKF 81297 [36].
• After 8-17 days' withdrawal, rats received an intra-mPFC microinjection of the full D1 agonist, SKF 81297: 0, 0.03, 0.1 or 0.3 microg/side followed by an i.p. saline or cocaine injection (15 mg/kg, i.p.). The target sites were either the dorsal or ventral mPFC [37].
• Just prior to reinstatement by immobilization stress or a cocaine priming injection (5 mg/kg, i.p.), a microinjection of the D1-like receptor antagonist SCH 23390 (0.01, 0.1 or 1.0 microg/side), or the D1-like receptor agonist SKF 81297 (0.1, 0.3 or 1.0 microg/side) was given into the medial prefrontal cortex [38].
• Here, we examined the effects of local application of a dopamine Type I (D(1)) receptor-specific agonist, SKF 81297, in the PFC on the chronic-stress-induced depressive state using a rotarod test [39].

References