Methylphenidates mechanism of action in the release of dopamine and norepinephrine is fundamentally different from most other phenethylamine derivatives, as methylphenidate is thought to increase neuronal firing rate, whereas amphetamine reduces firing rate, but causes monoamine release by reversing the flow of the monoamines through monoamine transporters via a diverse set of mechanisms, including TAAR1 activation and modulation of VMAT2 function, among other mechanisms. The difference in mechanism of action between methylphenidate and amphetamine results in methylphenidate inhibiting amphetamines effects on monoamine transporters when they are co-administered.Methylphenidate has both dopamine transporter and norepinephrine transporter binding affinity, with the dextromethylphenidate enantiomers displaying a prominent affinity for the norepinephrine transporter. Both the dextrorotary and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT1A and 5HT2B subtypes, though direct binding to the serotonin transporter was not observed. A later study confirmed the d-threo-methylphenidate (dexmethylphenidate) binding to the 5HT1A receptor, but no significant activity on the 5HT2B receptor was found.Methylphenidate may protect neurons from the neurotoxic effects of Parkinsons disease and methamphetamine use disorder. The hypothesized mechanism of neuroprotection is through inhibition of methamphetamine-DAT interactions, and through reducing cytosolic dopamine, leading to decreased production of dopamine-related reactive oxygen species.The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate. The studied maximized daily dosage of OROS methyphenidate appears to be 144 mg/day. Pharmacokinetics
Methylphenidate taken by mouth has a bioavailability of 11–52% with a duration of action around 2–4 hours for instant release (i.e. Ritalin), 3–8 hours for sustained release (i.e.
They argue that the presence of this particular frequency of contractions can distinguish between voluntary contraction of these muscles and spontaneous involuntary contractions, and appears to more accurately correlate with orgasm as opposed to other metrics like heart rate that only measure excitation. They assert that they have identified "[t]he first objective and quantitative measure that has a strong correspondence with the subjective experience that orgasm ultimately is" and state that the measure of contractions that occur at a frequency of 8–13 Hz is specific to orgasm. They found that using this metric they could distinguish from rest, voluntary muscular contractions, and even unsuccessful orgasm attempts.Since ancient times in Western Europe, women could be medically diagnosed with a disorder called female hysteria, the symptoms of which included faintness, nervousness, insomnia, fluid retention, heaviness in abdomen, muscle spasm, shortness of breath, irritability, loss of appetite for food or sex, and "a tendency to cause trouble". Women considered suffering from the condition would sometimes undergo "pelvic massage" — stimulation of the genitals by the doctor until the woman experienced "hysterical paroxysm" (i.e., orgasm). Paroxysm was regarded as a medical treatment, and not a sexual release. The disorder has ceased to be recognized as a medical condition since the 1920s. Brain
There have been very few studies correlating orgasm and brain activity in real time. One study examined 12 healthy women using a positron emission tomography (PET) scanner while they were being stimulated by their partners.