Ketamine action

Marwah, J. El ectrophysiological studies of ketamine action in frog skeletal muscle. Neuropharmacoloqy 19 765-772, 1980. Marwah, J. Candidate mechanisms underlying phencyclidine-induced psychosis An electrophysiologica 1, behavioral and biochemical... 

Winters, W. D., Alcaraz, M., Cervantes, M. Y., and Guzman-Flores, C. (1973) The synergistic effect of reduced visual input on ketamine action The possible role of the pineal gland. Neuropharmacology, 12 407-416. 

The mechanism of PCP and ketamine action involves antagonism of a subset of receptors for the excitatory amino acid glutamate (Balazs et al., 2006). PCP is absorbed rapidly after smoking or injection, with peak blood concentrations noted 5-15 minutes after smoking. In contrast, peak concentrations are reached wo hours after oral administration. The drug remains in the system unmetabolized for more than nvo days, and PCP is detectable in urine for several weeks after a single use (Hawks Cliiang, 1986). 

Mice lacking the 8 subunit, which is mainly expressed in cerebellum and thalamus, display an attenuation of ssatrighting reflex time following the administration of the neurosteroids, alphaxalone and pregnanolone, while the responses to propofol, etomindate, ketamine and the benzodiazepine midazolam were unaffected. This demonstrates the role of GABAa receptors containing the 8 subunit for neurosteroid action. 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

At low doses, ketamine may result in impairment of attention, learning ability, and memory, and at high doses it has been associated with delirium, amnesia, impaired motor function, hypertension, depression, and respiratory depression (Krystal et al. 1994). Another mechanism of action appears to be a blocking of the reuptake of catecholamines. This effect leads to an increase in heart rate and blood pressure (Reich and Silvay 1989). 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

The chemical structure of ketamine is similar to that of the potent psychedelic PCP (Figure 6.2). Not surprisingly, ketamine produces many psychedelic effects that are similar to those produced by PCP. However, ketamine s effects are much shorter in duration—a trip on ketamine may last only 30-60 minutes, whereas a trip on PCP may last several hours. The onset of ketamine s actions is quite rapid (i.e., within minutes), especially if snorted or injected intravenously. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

Ketamine and also tiletamine are structurally and pharmacologically related to phencyclidine. Its mechanism of action is not well understood. It has been suggested that it blocks the membrane effects of the excitatory neurotransmitter glutamic acid. Ketamine produces dissociative anesthesia, which means that the patient seems to be awake but there are no responses to sensory stimuli. Ketamine, which can be administered IV or IM, has strong analgesic activity. It is especially indicated for interventions of short duration without any need for skeletal... 

Wang Y, Small DL, Stanimhovic DB, et al (1997) AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. Nature 389 502-504 Warncke T, Jorimi E, Stubhaug A (1997) Local treatment with the N-methyl-n-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action. Neurosci Lett 227 1-4... 

Ketamine is a cyclohexanone derivative whose pharmacological actions are quite different from those of the other IV anesthetics. The state of unconsciousness it produces is trancelike (i.e., eyes may remain open until deep anesthesia is obtained) and cataleptic it has frequently been characterized as dissociative (i.e., the patient may appear awake and reactive but does not respond to sensory stimuli). The term dissociative anesthesia is used to describe these qualities of profound analgesia, amnesia, and superficial level of sleep. 

The noncompetitive antagonists of glutamate include phencyclidine, ketamine, N-allylnormetazocine, dextromethorphan, and dyzolcipine. The action of these compounds depends on the previous opening situation of the channel. Unfortunately, some of these useful NMDA antagonists have a narrow therapeutic margin. This could explain the contradictory results of studies. 

If a (3-adrenoceptor antagonist is administered prior to sufficient ol-radrenoceptor blockade, a hypertensive episode may be precipitated with cardiac failure and pulmonary oedema. Most intravenous anaesthetic agents have been used safely, but ketamine is contraindicated. Sodium nitroprusside can be used to achieve arteriolar dilation. Esmolol, a pi-selective antagonist with very short duration of action, is administered intravenously to prevent cardiac arrhythmias intra-operatively. After tumour removal, volume administration should be aggressive to maintain haemodynamic stability, and a noradrenaline infusion may be required. 

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