lecture IX: glutamate and GABA

• AMPA receptors

• active = sodium influx

• NMDA

• active = Ca influx (for downstream signaling)

• requires glycine and glutamate bound

• memantine

• binds to the polar regions of the target site (NMDA receptor inhibitor)

• used to treat alzheimers

• GABA A receptor

• active = Cl influx (induces inhibitory effects)

• GABA B receptor

• inhibition of Ca influx (inhibitory effect)

• nipecotic acid

• inhibit GABA transporter found at the synaptic cleft. causes more buildup of GABA at the synaptic cleft = prolonged inhibition

• research use only

• tiagabine

• inhibit GABA transporter found at the synaptic cleft. causes more buildup of GABA at the synaptic cleft = prolonged inhibition

• clinical use

• vigabatrin

• inhbits GABA transaminase, causing prevention of degradation of GABA, causing more GABA to buildup in the cleft

• GHB

• GABA feedback mechanism. its receptor is found at the pre-synapse. when bound, it reduces the release of GABA (dis-inhibitory effect)

• has euphoric effects (double negative = positive)

• used to treat narcolepsy

• granisetron/zofran

• 5-HT3 antagonists, used to treat nausea + vomiting

• benzodiazepines

• promote opening of GABA A receptors, allowing better inhibition (more anion influx). this helps with sedation, anxiety, and regualtion involuntary movements

• substance p (p = puke)

• binds neurokinin receptors (NK receptors) is highly expressed in the medulla; promotes vomiting

• aprepitant

• a NK-1R antagonist, used to prevent vomiting in cancer patients

• hypocretin (orexin)

• used to promote wakefulness

• inhabited, can cause narcolepsy

• AVP/ADH

• binds vasopressin I (blood) and II (kidney)

• bound = reduced vessel diameter

• increases water retention = concentrated urine = reduced serum sodium (hypotonic = swelled cells, die)

• conivaptan

• (V2 antagonist) to treat hyponatremia (low sodium in blood)