Taken together, stronger serotonin reuptake inhibition has consistently been associated with greater alleviation of OCD symptoms, and since clomipramine, at the clinical dosages in which it is employed, is effectively the strongest SRI used medically (see table above), this may underlie its unique effectiveness in the treatment of OCD. In addition to serotonin reuptake inhibition, clomipramine is also a mild but clinically significant antagonist of the dopamine D1, D2, and D3 receptors at high concentrations. Addition of antipsychotics, which are potent dopamine receptor antagonists, to SSRIs, has been found to significantly augment their effectiveness in the treatment of OCD. As such, besides strong serotonin reuptake inhibition, clomipramine at high doses might also block dopamine receptors to treat OCD symptoms, and this could additionally or alternatively be involved in its possible effectiveness advantage over SSRIs.Although clomipramine is probably more effective in the treatment of OCD compared to SSRIs, it is greatly inferior to them in terms of tolerability and safety due to its lack of selectivity for the SERT and promiscuous pharmacological activity. In addition, clomipramine has high toxicity in overdose and can potentially result in death, whereas death rarely, if ever, occurs with overdose of SSRIs. It is for these reasons that clomipramine, in spite of potentially superior effectiveness to SSRIs, is now rarely used as a first-line agent in the treatment of OCD, with SSRIs being used as first-line therapies instead and clomipramine generally being reserved for more severe cases and as a second-line agent. Pharmacokinetics
The oral bioavailability of clomipramine is approximately 50%.
He starts intoning "Alka-Seltzer, Alka-Seltzer..." Soon, the other hundreds of inmates do the same. (The commercial became so popular that several weeks later, Raft appeared as a guest on The Tonight Show Starring Johnny Carson. Raft told Carson that it took more than 7 hours to tape the 30-second commercial. Raft was enraged by the end of the day, thus making his inmate portrayal that much more convincing for the final editing. The film crew gave Raft his crumpled tin cup, which he showed to Carson and the audience.An animated mid-1960s commercial, animated by R. O. Blechman, shows a man and his own stomach sitting opposite each other in chairs, having an argument moderated by their therapist in a voiceover. The stomach (voiced by Gene Wilder) accuses the man of purposely trying to irritate it. The man accuses his stomach of complaining too much about the foods he likes. The therapist suggests Alka-Seltzer, and further suggests that the two must take care of each other. The closing words are of the stomach saying to the man: "Well, Ill try — if you will. "Alka-Seltzer had a series of commercials during the mid-1960s that used a song called "No Matter What Shape (Your Stomachs In)". A different version was recorded by The T-Bones and was released as a single, which became a hit in 1966. The ads featured only the midsections (no faces) of people of all shapes and sizes.